CFH

Summary

CFH (complement factor H, HGNC:4883) is a protein-coding gene on chromosome 1q31.3, encoding Complement factor H (P08603). Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.

This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 3075 — RefSeq curated summary.

At a glance

• Gene–disease (curated): C3 glomerulonephritis (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 79 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 1,655 total — 86 pathogenic, 72 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 24 tissues, sQTL in 25 (q < 0.05)
• Phenotypes (HPO): 89
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_000186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4883
Approved symbol	CFH
Name	complement factor H
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	HUS, FHL1, ARMS1, ARMD4
Ensembl gene	ENSG00000000971
Ensembl biotype	protein_coding
OMIM	134370
Entrez	3075

Gene structure

Transcript identifiers

Ensembl transcripts: 102 — 57 protein_coding, 32 nonsense_mediated_decay, 10 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000367429

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2

ENST00000367429, ENST00000359637, ENST00000466229, ENST00000470918, ENST00000496761, ENST00000630130, ENST00000695968, ENST00000695969, ENST00000695970, ENST00000695971, ENST00000695972, ENST00000695973, ENST00000695974, ENST00000695975, ENST00000695976, ENST00000695977, ENST00000695978, ENST00000695979, ENST00000695980, ENST00000695981, ENST00000695983, ENST00000695984, ENST00000695986, ENST00000695987, ENST00000695990, ENST00000696018, ENST00000696019, ENST00000696020, ENST00000696021, ENST00000696022, ENST00000696023, ENST00000696024, ENST00000696025, ENST00000696026, ENST00000696027, ENST00000696028, ENST00000696029, ENST00000696030, ENST00000696031, ENST00000883397, ENST00000883398, ENST00000883399, ENST00000883400, ENST00000883401, ENST00000883402, ENST00000883403, ENST00000883404, ENST00000883405, ENST00000883406, ENST00000883407, ENST00000883408, ENST00000883409, ENST00000883410, ENST00000883411, ENST00000883412, ENST00000883413, ENST00000883414, ENST00000883415, ENST00000955307, ENST00000955308, ENST00000955310, ENST00000955311, ENST00000986068, ENST00000986069, ENST00000986071, ENST00000986072, ENST00000986073, ENST00000986074, ENST00000986076, ENST00000986077, ENST00000986078, ENST00000986079, ENST00000986080, ENST00000986081, ENST00000986084, ENST00000986086, ENST00000986087, ENST00000986088, ENST00000986090, ENST00000986091, ENST00000986092, ENST00000986093, ENST00000986095, ENST00000986096, ENST00000986097, ENST00000986098, ENST00000986099, ENST00000986101, ENST00001025734, ENST00001109134, ENST00001109135, ENST00001109136, ENST00001109137, ENST00001114690, ENST00001117908, ENST00001117909, ENST00001117910, ENST00001117911, ENST00001117912, ENST00001117913, ENST00001130668, ENST00001145852

RefSeq mRNA: 2 — MANE Select: NM_000186 NM_000186, NM_001014975

CCDS: CCDS1385, CCDS53452

Canonical transcript exons

ENST00000367429 — 22 exons

Exon	Start	End
ENSE00000469053	196741875	196742051
ENSE00000791016	196679623	196679793
ENSE00000791028	196740619	196740792
ENSE00001134426	196672978	196673163
ENSE00003520851	196689420	196689614
ENSE00003536337	196743452	196743628
ENSE00003540360	196685064	196685237
ENSE00003570710	196747111	196747504
ENSE00003602895	196745817	196745999
ENSE00003623048	196690063	196690239
ENSE00003631361	196737475	196737660
ENSE00003965659	196726470	196726652
ENSE00003965663	196677476	196677667
ENSE00003965667	196715593	196715769
ENSE00003965669	196726761	196726940
ENSE00003965686	196673857	196673962
ENSE00003965703	196728346	196728522
ENSE00003965709	196736824	196737006
ENSE00003965711	196713735	196713917
ENSE00003965712	196675989	196676065
ENSE00003965720	196725121	196725297
ENSE00003965817	196652043	196652175

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7070 / max 1860.6969, expressed in 1116 samples.

Highest expression (Bgee): urethra, calcaneal tendon, coronary artery, lobe of liver, saphenous vein.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFH is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 25 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 49 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	sqtl	1.4e-78	+1.42	1:196851104:C:A
Nerve Tibial	eqtl	2.7e-21	-0.34	1:196545046:A:T
Artery Tibial	sqtl	2.3e-20	+0.55	1:196677131:A:G
Spleen	sqtl	1.3e-18	+1.18	1:196851104:C:A
Skin Sun Exposed Lower leg	sqtl	1.4e-14	+0.48	1:196741786:T:C
Nerve Tibial	sqtl	6.5e-14	+0.44	1:196846733:C:T
Adipose Subcutaneous	sqtl	2.6e-12	-0.48	1:196706226:G:A
Esophagus Muscularis	eqtl	3.2e-12	-0.24	1:196421983:C:G
Cells Cultured fibroblasts	eqtl	2.0e-10	+0.18	1:196651787:C:T
Artery Tibial	eqtl	3.2e-09	-0.22	1:196544193:A:G
Artery Aorta	eqtl	6.3e-09	+0.25	1:196394414:G:A
Adipose Subcutaneous	eqtl	7.8e-09	+0.24	1:196447806:GAC:G
Skin Not Sun Exposed Suprapubic	sqtl	1.2e-08	+0.43	1:196846733:C:T
Ovary	sqtl	7.0e-08	-1.24	1:196686150:C:G
Thyroid	sqtl	1.0e-07	+0.36	1:196851990:G:A
Heart Atrial Appendage	eqtl	1.4e-07	-0.19	1:196391465:A:T
Lung	eqtl	2.4e-07	-0.18	1:196422065:C:T
Artery Coronary	eqtl	7.2e-07	+0.32	1:196556184:A:C
Artery Aorta	sqtl	1.1e-06	+0.45	1:196695375:C:T
Breast Mammary Tissue	sqtl	1.9e-06	+0.33	1:196731784:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
7503	25.2986	1115
7502	0.3596	194
201860	0.0488	21

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	99.68	gold quality
calcaneal tendon	UBERON:0003701	99.47	gold quality
right coronary artery	UBERON:0001625	99.45	gold quality
right lobe of liver	UBERON:0001114	99.43	gold quality
saphenous vein	UBERON:0007318	99.25	gold quality
synovial joint	UBERON:0002217	99.07	gold quality
coronary artery	UBERON:0001621	99.03	gold quality
left coronary artery	UBERON:0001626	99.01	gold quality
parietal pleura	UBERON:0002400	98.98	gold quality
popliteal artery	UBERON:0002250	98.88	gold quality
tibial artery	UBERON:0007610	98.88	gold quality
gall bladder	UBERON:0002110	98.87	gold quality
right atrium auricular region	UBERON:0006631	98.86	gold quality
cardiac atrium	UBERON:0002081	98.61	gold quality
liver	UBERON:0002107	98.48	gold quality
aorta	UBERON:0000947	98.45	gold quality
right ovary	UBERON:0002118	98.44	gold quality
left ovary	UBERON:0002119	98.37	gold quality
tibial nerve	UBERON:0001323	98.36	gold quality
vena cava	UBERON:0004087	98.32	gold quality
palpebral conjunctiva	UBERON:0001812	98.18	gold quality
descending thoracic aorta	UBERON:0002345	98.13	gold quality
ascending aorta	UBERON:0001496	97.95	gold quality
pleura	UBERON:0000977	97.93	gold quality
thoracic aorta	UBERON:0001515	97.93	gold quality
minor salivary gland	UBERON:0001830	97.87	gold quality
layer of synovial tissue	UBERON:0007616	97.80	gold quality
right lobe of thyroid gland	UBERON:0001119	97.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.53	gold quality
pericardium	UBERON:0002407	97.47	gold quality
left lobe of thyroid gland	UBERON:0001120	97.36	gold quality
skin of hip	UBERON:0001554	97.25	gold quality
tendon	UBERON:0000043	97.14	gold quality
rectum	UBERON:0001052	97.07	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.02	gold quality
thyroid gland	UBERON:0002046	96.95	gold quality
mucosa of stomach	UBERON:0001199	96.84	gold quality
trachea	UBERON:0003126	96.41	gold quality
right lung	UBERON:0002167	96.40	gold quality
visceral pleura	UBERON:0002401	96.40	gold quality
adipose tissue	UBERON:0001013	96.23	gold quality
skin of leg	UBERON:0001511	96.16	gold quality
mouth mucosa	UBERON:0003729	95.97	gold quality
penis	UBERON:0000989	95.90	gold quality
connective tissue	UBERON:0002384	95.88	gold quality
germinal epithelium of ovary	UBERON:0001304	95.83	gold quality
colonic epithelium	UBERON:0000397	95.71	gold quality
upper leg skin	UBERON:0004262	95.66	gold quality
saliva-secreting gland	UBERON:0001044	95.60	gold quality
urinary bladder	UBERON:0001255	95.48	gold quality
peritoneum	UBERON:0002358	95.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.48	gold quality
omental fat pad	UBERON:0010414	95.48	gold quality
dorsal root ganglion	UBERON:0000044	95.44	gold quality
upper lobe of left lung	UBERON:0008952	95.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.89	gold quality
pylorus	UBERON:0001166	94.83	gold quality
ovary	UBERON:0000992	94.78	gold quality
fundus of stomach	UBERON:0001160	94.77	gold quality
trigeminal ganglion	UBERON:0001675	94.68	gold quality
zone of skin	UBERON:0000014	94.64	gold quality
upper lobe of lung	UBERON:0008948	94.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.61	gold quality
mucosa of urinary bladder	UBERON:0001259	94.50	gold quality
cardia of stomach	UBERON:0001162	94.45	gold quality
pharyngeal mucosa	UBERON:0000355	94.23	gold quality
upper arm skin	UBERON:0004263	94.19	gold quality
cartilage tissue	UBERON:0002418	94.04	gold quality
periodontal ligament	UBERON:0008266	93.87	gold quality
mammalian vulva	UBERON:0000997	93.66	gold quality
tendon of biceps brachii	UBERON:0008188	93.58	gold quality
body of tongue	UBERON:0011876	93.52	gold quality
lower esophagus	UBERON:0013473	93.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.47	gold quality
skin of abdomen	UBERON:0001416	93.27	gold quality
superficial temporal artery	UBERON:0001614	93.12	gold quality
choroid plexus epithelium	UBERON:0003911	93.12	gold quality
nasal cavity mucosa	UBERON:0001826	93.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.00	gold quality
lower esophagus mucosa	UBERON:0035834	92.59	gold quality
esophagus	UBERON:0001043	92.55	gold quality
lung	UBERON:0002048	92.55	gold quality
oral cavity	UBERON:0000167	92.54	gold quality
left adrenal gland	UBERON:0001234	92.24	gold quality
right adrenal gland	UBERON:0001233	92.21	gold quality
heart	UBERON:0000948	92.06	gold quality
tibia	UBERON:0000979	91.99	gold quality
left adrenal gland cortex	UBERON:0035825	91.98	gold quality
caecum	UBERON:0001153	91.97	gold quality
small intestine	UBERON:0002108	91.84	gold quality
adrenal cortex	UBERON:0001235	91.70	gold quality
right adrenal gland cortex	UBERON:0035827	91.67	gold quality
adrenal gland	UBERON:0002369	91.59	gold quality
esophagus mucosa	UBERON:0002469	91.57	gold quality
vermiform appendix	UBERON:0001154	91.40	gold quality
smooth muscle tissue	UBERON:0001135	91.38	gold quality
olfactory bulb	UBERON:0002264	91.36	gold quality
stomach	UBERON:0000945	91.18	gold quality
lymph node	UBERON:0000029	91.17	gold quality
endocervix	UBERON:0000458	91.13	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	1344.00
E-CURD-119	yes	910.08
E-GEOD-131882	yes	891.53
E-MTAB-8142	yes	769.41
E-HCAD-1	yes	84.20
E-MTAB-8410	yes	61.00
E-HCAD-11	yes	42.79
E-CURD-46	yes	34.26
E-HCAD-4	yes	16.10
E-CURD-112	yes	13.34
E-GEOD-130148	yes	9.44
E-HCAD-35	yes	8.40
E-GEOD-84465	yes	7.22
E-MTAB-10553	yes	5.89
E-MTAB-7381	no	75.43

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 62 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	1585.8	not detected
Urinary bladder	tissue	143.9	not detected
Ovary	tissue	139.7	not detected
Gallbladder	tissue	112.7	not detected
Heart muscle	tissue	95.5	not detected
Tongue	tissue	75.8
Rectum	tissue	70.2	not detected
Cervix	tissue	70.1	not detected
Breast	tissue	65.6	not detected
Adipose tissue	tissue	61.8	not detected
Esophagus	tissue	50.8	not detected
Lung	tissue	49.7	not detected
Colon	tissue	48.6	not detected
Small intestine	tissue	43.9	not detected
Choroid plexus	tissue	43.6
Adrenal gland	tissue	42.7	not detected
Stomach 1	tissue	40.9	not detected
Skin 1	tissue	39.8	low
Thyroid gland	tissue	29.5	not detected
Vagina	tissue	28.8	not detected
Appendix	tissue	28.8	not detected
Salivary gland	tissue	28.3	not detected
Smooth muscle	tissue	27.4	not detected
Duodenum	tissue	26.5	not detected
Lymph node	tissue	25.4	not detected
Kidney	tissue	23.4	not detected
Tonsil	tissue	22.5	not detected
Seminal vesicle	tissue	21.8	not detected
Placenta	tissue	21.4	not detected
Epididymis	tissue	19.2	not detected
Prostate	tissue	18.8	not detected
Cerebral cortex	tissue	15.5	not detected
Pituitary gland	tissue	15.4
Spleen	tissue	12.7	not detected
Pancreas	tissue	12.3	not detected
Testis	tissue	12.0	high
Thymus	tissue	11.2
Endometrium 1	tissue	10.2	not detected
Thalamus	tissue	9.7
Fallopian tube	tissue	9.5	not detected
Skeletal muscle	tissue	9.4	not detected
Basal ganglia	tissue	8.2	not detected
Pons	tissue	6.9
Cerebellum	tissue	6.9	not detected
Spinal cord	tissue	6.4
Medulla oblongata	tissue	6.2
Midbrain	tissue	5.7
Hypothalamus	tissue	5.7
Parathyroid gland	tissue	5.5	not detected
Substantia nigra	tissue	5.2
Putamen	tissue	5.1
Amygdala	tissue	5.0
Hippocampal formation	tissue	4.8
Hippocampus	tissue	4.2	not detected
Retrosplenial cortex	tissue	4.2
Retina	tissue	3.5
Nucleus accumbens	tissue	3.2
Occipital cortex	tissue	2.7
Locus coeruleus	tissue	2.6
Postcentral gyrus	tissue	2.6

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Blood vessel (286.7), Anterior insular cortex, dorsal (15.5), Anterior thalamic nucleus, ventral (9.7), Posterior thalamic nucleus (9.4), Cerebellar white matter (8.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOS, FOXA2, FOXO3, JUN, NFKB, SIRT1, STAT1

miRNA regulators (miRDB)

Targeting CFH by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

17 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-3907	96.76	65.04	662

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.43, missense Z 1.47 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000367429 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:196,652,118–196,679,651	260 / 263.3	0.99	no
1:196,679,652–196,690,100	167 / 228.0	0.73	no
1:196,690,101–196,743,557	830 / 821.4	1.01	no
1:196,743,558–196,747,310	123 / 185.3	0.66	no

Literature-anchored findings (GeneRIF, showing 40)

• This paper (PMID 10781834) was the first to describe the detailed structure of the human CFH gene. (PMID:10781834)
• Three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) enhance factor H’s cofactor activity enabling MCP-like cellular evasion of complement-mediated attack. (PMID:11825898)
• molecular modelling of the C-terminal domains of factor H of human complement: a correlation between haemolytic uraemic syndrome and a predicted heparin binding site (PMID:11851332)
• acts as adrenomedullin binding protein - review (PMID:11921353)
• Recombinant factor H with deletions at the carboxyl-terminal end loses the ability to control the spontaneous activation of the alternative complement pathway on host-like surfaces, a functional defect that leads to acute renal failure in HUS. (PMID:12391176)
• structural and functional characterization of three different factor H proteins purified from the plasma of patients with atypical hemolytic uremic syndrome who carry the factor H mutations W1183L, V1197A, or R1210C (PMID:12424708)
• The site and putative residues on factor H (FH) essential for the interaction of the C-terminal end of FH with C3d, C3b, and heparin have been identified; the heparin- and C3d-binding sites are overlapping. (PMID:12471127)
• two specific binding sites for adrenomedullin were found in factor H (PMID:12630812)
• Screening for factor H gene (FH1) mutations contributes to the classification of atypical haemolytic uraemic syndrome (aHUS). (PMID:12960213)
• promoted entry of Fba(+) group A streptococci into epithelial cells in a dose-dependent manner but did not affect invasion by an isogenic fba mutant (PMID:14638802)
• CFH deficiency my favor acute allograft glomerulopathy. (PMID:14974950)
• Review. Factor H is an essential regulatory protein for complement homeostasis in plasma & for the protection of bystander host cells & tissues from damage by complement activation. Genetic & structural data delineate the functional domains responsible. (PMID:15163532)
• Complement factor H contributes to the control mechanism of in situ complement activation and prevents renal damage in idiopathic membranous nephropathy. (PMID:15331938)
• Human complement regulatory factor H binds to Streptococcal pyogenes M18 surface protein Emm18. (PMID:15557185)
• Binding to platelets is mediated by the C-terminal region of factor H and factor H mutated at the C-terminus exhibited reduces binding (PMID:15634279)
• Factor H is cleaved by a dermatan sulfate-mediated protease identified in blood. (PMID:15749837)
• A novel nucleotide substitution 3254T–>C causing a Ser1061Pro substitution in the short consensus repeat SCR18was found in a girl with hemolytic uremic sundrome. (PMID:15754282)
• a common coding variant, Y402H, that significantly increases the risk for age-related macular degeneration (AMD)with odds ratios between 2.45 and 5.57 was revealed; this common variant likely explains approximately 43% of AMD in older adults (PMID:15761120)
• tested single-nucleotide polymorphisms in CFH for association with age-related macular degeneration (AMD) in two case-control populations; possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold (PMID:15761121)
• identified a tyrosine-histidine polymorphism in which the histidine variant almost always occurs in the context of the age-related macular degeneration risk haplotype (PMID:15761122)
• there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical haemolytic-uraemic syndrome (PMID:15784724)
• Binding of CFH to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site. (PMID:16192651)
• no association of the complement factor H Y402H gene polymorphism with risk of incident thromboembolic events, nor with baseline levels of C-reactive protein (PMID:16229850)
• Three heparin-binding sites were identified in complement factor H1. (PMID:16263173)
• results suggest that the interaction with pneumococci PspC contributes to pneumococcal virulence. (PMID:16267773)
• Deficiency of and mutations and variations in the complement factor H (CFH) gene are associated with the development of membranoproliferative glomerulonephritis type II. (PMID:16299065)
• Keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-gamma. (PMID:16310045)
• These results suggest the contribution of the Y402H polymorphism of the CFH gene to exudative AMD susceptibility also in the French population (PMID:16379025)
• Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome. (PMID:16386793)
• The CFH Y402H variant is strongly associated with both GA(geographic atrophy) and CNV (choroidal neovascularization) in the U.K. population. (PMID:16431947)
• gene conversion is responsible for functionally significant CFH mutations in atypical hemolytic uremic syndrome (PMID:16470555)
• Two different factor H mutations associated with atypical hemolytic uremic syndrome were examined: in one, factor H accumulated in cells, and in the other, membrane binding was reduced. (PMID:16528247)
• three-dimensional solution structure of the C-terminal module pair of factor H (PMID:16533809)
• Four previously found haplotypes and one additional haplotype were found. Haplotype frequencies were significantly different from those in found Americans affected with macular degeneration. Two were risk factors and one was protective. (PMID:16541016)
• CFH gene determines susceptibility to myocardial infarction. HisHis homozygotes had a hazard ratio of 1.77 for myocardial infarction. (PMID:16630992)
• CFH does not appear to be a primary hereditary contributor to age-related macular degeneration {ARMD} in Japanese, and the absence of CFH contribution to ARMD in Japanese may correlate with the findings in ethnic differences of ARMD phenotypes. (PMID:16710702)
• No evidence was found to associate the complement factor H Y402H gene polymorphism with coronary artery disease and atherosclerosis. (PMID:16730735)
• When bound to Neisseria meningitidis, factor H retains its activity as cofactor of alternative complement pathway factor I and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. (PMID:16751403)
• Results describe age-related macular degeneration (AMD) genetic risk factors through identification of polymorphisms in ERCC6 and in complement factor H. (PMID:16754848)
• Factor H (fH) binds to an approximately 29-kDa outer membrane protein on Neisseria meningitidis identified as GNA1870; binding of down-regulator protein fH correlates with levels of neisserial GNA1870 expression. (PMID:16785547)

Cross-species orthologs

0 orthologs

Paralogs (39): SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88385) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 66 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating complement protein level	4
abnormal retina morphology	3
premature death	3
glomerulonephritis	2
thrombocytopenia	2
hematuria	2
abnormal renal glomerulus morphology	2
increased blood urea nitrogen level	2
expanded mesangial matrix	2
abnormal kidney thrombosis	2
renal glomerular protein deposits	2
schistocytosis	1
abnormal kidney vasculature morphology	1
hindlimb paralysis	1
abnormal retina photoreceptor morphology	1
decreased body size	1
circling	1
anemia	1
intracerebral hemorrhage	1
abnormal kidney morphology	1
abnormal blood coagulation	1
reticulocytosis	1
abnormal retina vasculature morphology	1
albuminuria	1
decreased hemoglobin content	1

+41 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mus musculus	Q6P1D5	80.8%	Diamond
Bos taurus	Q28085	61.9%	Diamond
Sus scrofa	Q03472	60.2%	Diamond
Drosophila melanogaster	Q09101	40.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CFHR3	protein-coding	10878
KCNT2	protein-coding	343450
MIR4735	ncRNA	100616363
CFHR1	protein-coding	3078
LINC01724	ncRNA	105371673
CFHR4	protein-coding	10877

Protein

Protein identifiers

Complement factor H — P08603 (reviewed: P08603)

Alternative names: H factor 1

All UniProt accessions (26): P08603, A0A0D9SG88, A0A8Q3SI55, A0A8Q3SI73, A0A8Q3SI76, A0A8Q3SI78, A0A8Q3SI99, A0A8Q3SIB6, A0A8Q3SIC3, A0A8Q3SID7, A0A8Q3SID8, A0A8Q3SIE0, A0A8Q3SIE8, A0A8Q3SJ41, A0A8Q3WKW2, A0A8Q3WKW3, A0A8Q3WKW6, A0A8Q3WKW7, A0A8Q3WKX0, A0A8Q3WKX4, A0A8Q3WL05, A0A8Q3WLF7, A0A8Q3WLY2, A0A8Q3WM65, A0A8Q3WM71, Q5TFM2

UniProt curated annotations — full annotation on UniProt →

Function. Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces. Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop. As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b. In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed. (Microbial infection) In the mosquito midgut, binds to the surface of parasite P.falciparum gametocytes and protects the parasite from alternative complement pathway-mediated elimination.

Subunit / interactions. Homodimer. Also forms homooligomers. Interacts with complement protein C3b; this interaction inhibits complement activation. Interacts with complement protein C3d. Interacts with CR3/ITGAM; this interaction mediates adhesion of neutrophils to pathogens leading to pathogen clearance. Interacts with complement factor I. (Microbial infection) Interacts with West nile virus non-structural protein 1 (NS1); this interaction leads to the degradation of C3. (Microbial infection) Interacts with C.albicans GPD2; the interaction is direct and leads to the degradation of C3 which enables the pathogen to evade the host innate immune system. (Microbial infection) Interacts with Neisseria meningitidis protein fHbp. (Microbial infection) Interacts with Borrelia burgdorferi outer surface protein E/OspE; this interaction recruits complement regulator factor H onto the bacterial surface to evade complement-mediated cell lysis. (Microbial infection) Interacts with Streptococcus pneumoniae protein virulence factor choline-binding protein A/CbpAN; this interaction enables Streptococcus pneumoniae to evade surveillance by human complement system. (Microbial infection) Interacts with Staphylococcus aureus surface protein serine-aspartate repeat protein E/SdrE; this interaction sequesters CFH on the surface of S.aureus for complement evasion. (Microbial infection) Interacts with Staphylococcus aureus protein Sbi; this interaction inhibits the complement activation of the alternative pathway. (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits CFH onto the merozoite surface preventing complement-mediated cell lysis. The interaction does not affect CFH activity. Interacts (via sushi 6-7 domains) with P.falciparum (strain NF54) GAP50; the interaction occurs in the vector mosquito midgut at the surface of the activated parasite gametocytes; the interaction protects the parasite from alternative complement pathway-mediated elimination. (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits FHL-1 isoform onto the merozoite surface preventing complement-mediated cell lysis. The interaction does not affect FHL-1 isoform activity. Interacts (via sushi 6-7 domains) with P.falciparum (strain NF54) GAP50; the interaction occurs in the vector mosquito midgut at the surface of the activated parasite gametocytes; the interaction protects the parasite from alternative complement pathway-mediated elimination.

Subcellular location. Secreted.

Tissue specificity. Expressed in the retinal pigment epithelium (at protein level). CFH is one of the most abundant complement components in blood where the liver is the major source of CFH protein in vivo. in addition, CFH is secreted by additional cell types including monocytes, fibroblasts, or endothelial cells.

Post-translational modifications. Sulfated on tyrosine residues. According to a report, Asn-217 is not glycosylated. Another study observed glycosylation at this position.

Disease relevance. Basal laminar drusen (BLD) [MIM:126700] Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss. The gene represented in this entry is involved in disease pathogenesis. Complement factor H deficiency (CFHD) [MIM:609814] A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. The disease is caused by variants affecting the gene represented in this entry. Hemolytic uremic syndrome, atypical, 1 (AHUS1) [MIM:235400] An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Macular degeneration, age-related, 4 (ARMD4) [MIM:610698] A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. Sushi 1-3 domain represents the minimal unit capable of cofactor activity. The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20.

Isoforms (2)

UniProt ID	Names	Canonical?
P08603-1	1	yes
P08603-2	2, FHL-1

RefSeq proteins (2): NP_000177, NP_001014975 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR051503	ComplSys_Reg/VirEntry_Med	Family

Pfam: PF00084

UniProt features (271 total): strand 105, sequence variant 59, disulfide bond 40, helix 22, domain 20, glycosylation site 9, mutagenesis site 5, sequence conflict 4, turn 3, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

showing 30 of 51 structures by resolution:

PDB	Title	Method	Resolution (Å)
1HAQ	FOUR MODELS OF HUMAN FACTOR H DETERMINED BY SOLUTION SCATTERING CURVE-FITTING AND …	SOLUTION SCATTERING	0
3GAU	Solution structure of Human Complement Factor H in 50 mM NaCl buffer	SOLUTION SCATTERING	0
3GAV	Solution structure of Human Complement Factor H in 137 mM NaCl buffer	SOLUTION SCATTERING	0
3GAW	Solution structure of Human Complement Factor H in 250 mM NaCl buffer	SOLUTION SCATTERING	0
4K12	Structural Basis for Host Specificity of Factor H Binding by Streptococcus pneumoniae	X-RAY DIFFRACTION	1.08
3R62	Structure of complement regulator Factor H mutant, T1184R.	X-RAY DIFFRACTION	1.52
3KZJ	Structure of complement Factor H variant R1203A	X-RAY DIFFRACTION	1.65
2G7I	Structure of Human Complement Factor H Carboxyl Terminal Domains 19-20: a Basis for …	X-RAY DIFFRACTION	1.75
3SW0	Structure of the C-terminal region (modules 18-20) of complement regulator Factor H	X-RAY DIFFRACTION	1.8
6ATG	Insights to complement factor H recruitment by the borrelial CspZ protein as revealed by …	X-RAY DIFFRACTION	1.8
9MLU	FbaA with Factor H 6-7 domain	X-RAY DIFFRACTION	1.82
9MMX	M6 protein with Factor H 6-7 domain	X-RAY DIFFRACTION	1.9
3KXV	Structure of complement Factor H variant Q1139A	X-RAY DIFFRACTION	2
3OXU	Complement components factor H CCP19-20 and C3d in complex	X-RAY DIFFRACTION	2.1
4ONT	Ternary host recognition complex of complement factor H, C3d, and sialic acid	X-RAY DIFFRACTION	2.15
6ZH1	Crystal structure of complex between FH19-20 and FhbA protein from Borrelia hermsii	X-RAY DIFFRACTION	2.2
4ZH1	Complement factor H in complex with the GM1 glycan	X-RAY DIFFRACTION	2.24
9MMU	M5 protein with Factor H 6-7 domain	X-RAY DIFFRACTION	2.25
2XQW	Structure of Factor H domains 19-20 in complex with complement C3d	X-RAY DIFFRACTION	2.31
4AYI	Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria …	X-RAY DIFFRACTION	2.31
2UWN	Crystal structure of Human Complement Factor H, SCR domains 6-8 (H402 risk variant), in …	X-RAY DIFFRACTION	2.35
2W80	Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs …	X-RAY DIFFRACTION	2.35
2W81	Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs …	X-RAY DIFFRACTION	2.35
3RJ3	Complement components factor H CCP19-20 (S1191L mutant) and C3D in complex	X-RAY DIFFRACTION	2.35
4AYD	Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria …	X-RAY DIFFRACTION	2.4
2V8E	Crystal structure of Human Complement Factor H, SCR domains 6-8 (H402 risk variant), in …	X-RAY DIFFRACTION	2.5
7ZJM	Crystal structure of a complex between CspZ from Borrelia burgdorferi strain B408 and …	X-RAY DIFFRACTION	2.59
7WKI	Structure of the ultra-affinity complex between CFH and a nanobody	X-RAY DIFFRACTION	2.6
2WII	Complement C3b in complex with factor H domains 1-4	X-RAY DIFFRACTION	2.7
4AYE	Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria …	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08603-F1	78.54	0.01

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7WKI

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, Human disease related genes, Primary immunodeficiency, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (40)

Type	Positions
Disulfide bond	21–66, 52–80, 85–129, 114–141, 146–192, 178–205, 210–251, 237–262, 267–309, 294–320, 325–374, 357–385, 389–431, 416–442, 448–494, 477–505, 509–553, 536–564, 569–611, 597–623, 630–673, 659–684, 691–733, 719–744, 753–792, 781–803, 811–853, 839–864, 870–915, 901–926, 931–973, 959–984, 989–1032, 1018–1043, 1048–1091, 1077–1102, 1109–1152, 1138–1163, 1167–1218, 1201–1228

Glycosylation sites (9)

Type	Positions
N-linked (glcnac…) (complex) asparagine	217, 882, 911, 1029
N-linked (glcnac…) asparagine	529, 718, 802, 822, 1095

Mutagenesis-validated functional residues (5)

Position	Phenotype
337	about 10% loss of heparin-binding.
341	about 20% loss of heparin-binding.
1182	about 50% loss of c3b binding.
1186	about 20% loss of c3b binding.
1188	about 50% loss of c3b binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-977606	Regulation of Complement cascade	curated
R-HSA-166658	Complement cascade	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—

MSigDB gene sets: 1073 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, LI_CISPLATIN_RESISTANCE_DN, GOBP_MEMBRANE_DEPOLARIZATION, ZHAN_LATE_DIFFERENTIATION_GENES_UP, MORF_FLT1, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TSENG_IRS1_TARGETS_UP, MORF_MSH3, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_INFLAMMATORY_RESPONSE, JAEGER_METASTASIS_DN, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY

GO Biological Process (10): proteolysis (GO:0006508), inflammatory response (GO:0006954), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), central nervous system myelination (GO:0022010), regulation of complement activation (GO:0030449), regulation of complement activation, alternative pathway (GO:0030451), regulation of complement-dependent cytotoxicity (GO:1903659), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (5): complement component C3b binding (GO:0001851), heparin binding (GO:0008201), identical protein binding (GO:0042802), heparan sulfate proteoglycan binding (GO:0043395), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), symbiont cell surface (GO:0106139)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Complement cascade	1
Innate Immune System	1
Immune System	1

GO top-level categories

32 GO namespaces:

Category	Terms
complement activation	2
cellular anatomical structure	2
protein metabolic process	1
defense response	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
innate immune response	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
regulation of immune effector process	1
regulation of humoral immune response	1
complement activation, alternative pathway	1
regulation of complement activation	1
regulation of innate immune response	1
regulation of cell killing	1
complement-dependent cytotoxicity	1
biological_process	1
immune response	1
defense response to symbiont	1
opsonin binding	1
complement binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
proteoglycan binding	1
binding	1
extracellular vesicle	1
extracellular region	1
other organism part	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
central nervous system myelination	BP	direct assay
complement activation	BP	direct assay
complement activation, alternative pathway	BP	direct assay
inflammatory response	BP	direct assay
proteolysis	BP	direct assay
regulation of complement activation	BP	direct assay
regulation of complement activation, alternative pathway	BP	direct assay
regulation of complement-dependent cytotoxicity	BP	direct assay
blood microparticle	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
symbiont cell surface	CC	direct assay
heparan sulfate proteoglycan binding	MF	direct assay
heparin binding	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,482 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFH	C3	P01024	978
CFH	CFI	P05156	969
CFH	ARMS2	P0C7Q2	953
CFH	C4A	P01028	867
CFH	C2	P06681	844
CFH	ADAMTS13	Q76LX8	840
CFH	C4A	P01028	827
CFH	PLEKHA1	Q9HB21	822
CFH	CFP	P27918	807
CFH	MYBPH	Q13203	801
CFH	THBD	P07204	794
CFH	HTRA1	Q92743	763
CFH	DGKE	P52429	759
CFH	C5	P01031	717
CFH	RBMS2	Q15434	706

IntAct

Human interaction partners of CFH in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
CRP	direct interaction	0.980	40
C3	protein cleavage	0.870	20
PTX3	direct interaction	0.820	27
APOE	physical association	0.670	8
ALB	direct interaction	0.670	7
CFHR1	colocalization	0.640	1
FMOD	direct interaction	0.620	4
CFHR3	physical association	0.400	1
KLHL18	physical association	0.400	1
EP300	physical association	0.370	1
SMAD3	physical association	0.370	1
TFAP2A	physical association	0.370	1
TFAP2C	physical association	0.370	1
VDR	physical association	0.370	1
YTHDC1	physical association	0.370	1
ZBTB16	physical association	0.370	1
DYRK1A	physical association	0.000	1
GRB2	physical association	0.000	1
LCOR	physical association	0.000	1
RSPH1	physical association	0.000	1

BioGRID (148 interactions; top human partners by supporting records): C3 (Reconstituted Complex; 2 records), CFHR3 (Affinity Capture-MS; 2 records), CREB1 (Affinity Capture-MS; 2 records), KLHL18 (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), ALB (Affinity Capture-MS), ALOX12B (Affinity Capture-MS), ANKRD12 (Affinity Capture-MS), ARHGEF40 (Affinity Capture-MS), ARL6IP4 (Affinity Capture-MS), ASB1 (Affinity Capture-MS), ATAD3A (Affinity Capture-MS), ATAD3B (Affinity Capture-MS), BMP1 (Affinity Capture-MS), BRAP (Affinity Capture-MS)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
PTX3	“up-regulates activity”	CFH	binding
CFH	“down-regulates activity”	C3	binding
CFH	“down-regulates activity”	CFB	binding
CFH	“down-regulates activity”	CRP	binding
CFH	“up-regulates activity”	CFI	binding
CFHR1	“down-regulates activity”	CFH	binding

Disease & clinical

Genetic variants

Variant evidence for CFH: 1,655 ClinVar records (158 pathogenic / likely pathogenic); 4 PharmGKB clinical annotations; 79 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,655 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	86
Likely pathogenic	72
Uncertain significance	855
Likely benign	356
Benign	49

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 158 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
16545	NM_000186.4(CFH):c.3572C>T (p.Ser1191Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
1450348	NM_000186.4(CFH):c.1873G>T (p.Glu625Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1163687	NM_000186.4(CFH):c.3610G>T (p.Gly1204Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1452931	NM_000186.4(CFH):c.1243del (p.Ala415fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4291415	NM_000186.4(CFH):c.1707C>A (p.Cys569Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4291419	NM_000186.4(CFH):c.1756C>T (p.Gln586Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
16551	NM_000186.4(CFH):c.1291T>A (p.Cys431Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1936765	NM_000186.4(CFH):c.2236+1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
2683637	NM_000186.4(CFH):c.3646ACA[1] (p.Thr1217del)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1343354	NM_000186.4(CFH):c.3322A>T (p.Lys1108Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1712431	NM_000186.4(CFH):c.3644G>T (p.Arg1215Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3381091	NM_000186.4(CFH):c.1673G>A (p.Trp558Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3575077	NM_000186.4(CFH):c.139del (p.Gln47fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3575324	NM_000186.4(CFH):c.1337-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
16542	NM_000186.4(CFH):c.3643C>G (p.Arg1215Gly)	Pathogenic	criteria provided, single submitter	3

Per-variant reference — Sugi Variant

Explore CFH’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 2,275):

Position(s)	Effect	Δscore	Sites
1:196685062–196685063	acceptor_loss	1.0000	6
1:196685238–196685239	donor_loss	1.0000	4
1:196689418	acceptor_gain	1.0000
1:196713918–196713919	donor_loss	1.0000	5
1:196725119	acceptor_gain	1.0000
1:196740789	donor_gain	1.0000
1:196747104	acceptor_gain	1.0000
1:196672976–196672977	acceptor_loss	0.9900	6
1:196673941	donor_gain	0.9900
1:196681720	donor_gain	0.9900

AlphaMissense

1,683 missense substitutions predicted likely pathogenic (of 8,066 scored), across 447 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F1199	8	0.911	0.990
W134	7	0.994	1.000
C114	7	0.993	0.997
C141	7	0.993	0.998
C129	7	0.990	0.998
C237	7	0.988	0.997
C192	7	0.987	0.996
C66	7	0.986	0.995
C85	7	0.986	0.994
C262	7	0.986	0.994
C52	7	0.985	0.996
C251	7	0.985	0.995
W314	7	0.985	0.998
C1032	7	0.985	0.994
C178	7	0.984	0.994
C309	7	0.983	0.997
C1091	7	0.982	0.995
C80	7	0.981	0.995
C792	7	0.981	0.992
W1037	7	0.981	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	0.000494

Disease associations

OMIM: gene MIM:134370 | disease phenotypes: MIM:126700, MIM:235400, MIM:609814, MIM:610698, MIM:612923

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
C3 glomerulonephritis	Definitive	Autosomal recessive
basal laminar drusen	Strong	Autosomal dominant	2
hemolytic uremic syndrome, atypical, susceptibility to, 1	Strong	Autosomal dominant	2
complement factor H deficiency	Strong	Autosomal recessive	2
Doyne honeycomb retinal dystrophy	Supportive	Autosomal dominant
dense deposit disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
C3 glomerulonephritis	Definitive	AR
atypical hemolytic-uremic syndrome	Definitive	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Atypical haemolytic uraemic syndrome	green
COVID-19 research	green
Membranoproliferative glomerulonephritis including C3 glomerulopathy	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Retinal disorders	green
Unexplained kidney failure in young people	green
Unexplained young onset end-stage renal disease	green

Mondo (11): basal laminar drusen (MONDO:0007472), hemolytic uremic syndrome, atypical, susceptibility to, 1 (MONDO:0009335), complement factor H deficiency (MONDO:0012350), age related macular degeneration 4 (MONDO:0012540), atypical hemolytic-uremic syndrome (MONDO:0016244), atypical hemolytic-uremic syndrome with I factor anomaly (MONDO:0013041), inherited retinal dystrophy (MONDO:0019118), membranoproliferative glomerulonephritis (MONDO:0002461), C3 glomerulonephritis (MONDO:0013892), Doyne honeycomb retinal dystrophy (MONDO:0007471), dense deposit disease (MONDO:0019736)

Orphanet (6): Immunodeficiency with factor H anomaly (Orphanet:200421), Atypical hemolytic uremic syndrome (Orphanet:2134), Familial drusen (Orphanet:75376), Shiga toxin-associated hemolytic uremic syndrome (Orphanet:90038), OBSOLETE: Inherited retinal disorder (Orphanet:71862), OBSOLETE: Atypical hemolytic uremic syndrome with I factor anomaly (Orphanet:93580)

HPO phenotypes

showing 60 of 89 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000529	Progressive visual loss
HP:0000572	Visual loss
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000979	Purpura
HP:0001058	Poor wound healing
HP:0001250	Seizure
HP:0001259	Coma
HP:0001269	Hemiparesis
HP:0001342	Cerebral hemorrhage
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001919	Acute kidney injury
HP:0001923	Reticulocytosis
HP:0001937	Microangiopathic hemolytic anemia
HP:0001945	Fever
HP:0001981	Schistocytosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002315	Headache
HP:0002381	Aphasia
HP:0002615	Hypotension
HP:0002718	Recurrent bacterial infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003077	Hyperlipidemia
HP:0003138	Increased blood urea nitrogen
HP:0003259	Elevated circulating creatinine concentration
HP:0003418	Back pain
HP:0003581	Adult onset
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003641	Hemoglobinuria
HP:0004324	Increased body weight
HP:0004722	Thickened glomerular basement membrane
HP:0004746	Glomerular subendothelial electron-dense deposits
HP:0005356	Decreased circulating complement factor I concentration
HP:0005369	Decreased circulating complement factor H concentration
HP:0005389	Depletion of components of the alternative complement pathway
HP:0005416	Decreased circulating complement factor B concentration
HP:0005421	Decreased circulating complement C3 concentration
HP:0005521	Disseminated intravascular coagulation
HP:0005575	Hemolytic-uremic syndrome
HP:0007401	Macular atrophy
HP:0007430	Generalized edema
HP:0007703	Abnormal retinal pigmentation
HP:0007754	Macular dystrophy
HP:0007793	Granular macular appearance
HP:0007937	Reticular pigmentary degeneration
HP:0007950	Peripapillary chorioretinal atrophy
HP:0008071	Maternal hypertension
HP:0008151	Prolonged prothrombin time

GWAS associations

showing 30 of 79 associations:

Study	Trait	p-value
GCST001884_12	Age-related macular degeneration	0.000000e+00
GCST003219_2	Advanced age-related macular degeneration	0.000000e+00
GCST003219_27	Advanced age-related macular degeneration	0.000000e+00
GCST010284_1	Age-related macular degeneration (MTAG)	0.000000e+00
GCST001100_8	Age-related macular degeneration	1e-261
GCST003219_6	Advanced age-related macular degeneration	6e-165
GCST000653_2	Age-related macular degeneration	4e-117
GCST010723_7	Early age-related macular degeneration	3e-114
GCST000653_6	Age-related macular degeneration	2e-111
GCST001579_1	Age-related macular degeneration (choroidal neovascularisation)	1e-108
GCST000652_6	Age-related macular degeneration	2e-76
GCST003219_5	Advanced age-related macular degeneration	1e-68
GCST001578_5	Age-related macular degeneration (geographic atrophy)	5e-67
GCST000806_1	Age-related macular degeneration	3e-64
GCST001571_2	Age-related macular degeneration	2e-47
GCST90019044_1	Complement factor H-related protein 3 levels	2e-47
GCST001979_1	Circulating myeloperoxidase levels (serum)	5e-41
GCST010306_1	Complement factor H binding to malondialdehyde	7e-41
GCST005359_17	Disease progression in age-related macular degeneration	3e-40
GCST002766_6	Exudative age-related macular degeneration	8e-38
GCST003219_34	Advanced age-related macular degeneration	8e-37
GCST005187_2	Matrix metalloproteinase-8 levels	2e-35
GCST001814_3	Age-related macular degeneration	7e-32
GCST001986_1	Age-related macular degeneration	1e-31
GCST001814_9	Age-related macular degeneration	2e-31
GCST90019044_2	Complement factor H-related protein 3 levels	1e-27
GCST003219_4	Advanced age-related macular degeneration	9e-26
GCST005358_3	Disease progression to choroidal neovascularization form in age-related macular degeneration	1e-25
GCST005360_1	Disease progression to geographic atrophy form in age-related macular degeneration	1e-25
GCST001987_2	Age-related macular degeneration (extreme sampling)	9e-24

EFO canonical traits (from GWAS)

16 canonical traits:

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004983	complement C3 measurement
EFO:0005243	myeloperoxidase measurement
EFO:0004713	FEV/FVC ratio
EFO:0008336	disease progression measurement
EFO:0008543	c3d:C3 ratio
EFO:0009281	choroidal thickness measurement
EFO:0009363	chronic central serous retinopathy
EFO:0008097	complement factor H measurement
EFO:0010742	protein binding measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0600055	complement factor H-related protein 2 measurement
EFO:0600056	complement factor H-related protein 3 measurement
EFO:0600057	complement factor H-related protein 4A measurement
EFO:0008098	complement factor H-related protein 5 measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D015432	Glomerulonephritis, Membranoproliferative	C12.050.351.968.419.570.363.615; C12.200.777.419.570.363.615; C12.950.419.570.363.615; C20.425
D058499	Retinal Dystrophies	C11.768.585.658
C563034	Basal Laminar Drusen *(supp.)*
C562875	Complement Factor H Deficiency *(supp.)*
C565196	Macular Degeneration, Age-Related, 4 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4629 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

4 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1061170	Dosage	3	bevacizumab	Macular Degeneration
rs800292	Efficacy	3	bevacizumab
rs1061170	Efficacy	4	Photodynamic therapy	Macular Degeneration
rs1061170	Efficacy	4	bevacizumab;ranibizumab	Macular Degeneration

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs800292	CFH	3	2.50	1	bevacizumab
rs1061170	CFH	3	1.75	3	bevacizumab;bevacizumab;ranibizumab;Photodynamic therapy

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

6 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1061170	bevacizumab	Dosage	Genotype CT is associated with increased dose of bevacizumab in people with Macular Degeneration as compared to genotype TT.	PMID:23204795
rs1061170	bevacizumab, ranibizumab	Efficacy	Genotype CC is associated with decreased response to bevacizumab and ranibizumab in people with Macular Degeneration as compared to genotypes CT + TT.	PMID:26411831
rs1061170	bevacizumab	Efficacy	Genotype CC is associated with decreased response to bevacizumab in people with Macular Degeneration as compared to genotypes CT + TT.	PMID:26439641
rs800292	bevacizumab	Efficacy	Genotype GG is associated with decreased response to bevacizumab in people with Macular Degeneration as compared to genotype AA.	PMID:22594510
rs1061170	Photodynamic therapy	Efficacy	Genotype TT is associated with decreased response to photodynamic therapy in people with Macular Degeneration as compared to genotypes CC + CT.	PMID:18292785
rs1061170	ranibizumab	Efficacy	Genotype TT is associated with increased response to ranibizumab in people with Macular Degeneration as compared to genotype CC.	PMID:22840423

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2-(methylsulfonyl)-[1,1-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	KI	0.15 nM

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	4
Air Pollutants	decreases expression, increases abundance	4
Cyclosporine	affects cotreatment, affects expression, decreases expression	4
Acetaminophen	decreases expression, increases expression	2
Progesterone	increases expression	2
Silicon Dioxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
zinc chromate	increases expression, increases abundance	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, increases expression, decreases expression	1
incobotulinumtoxinA	increases expression	1
trametinib	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Olanzapine	decreases phosphorylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL666763	Binding	In vitro activity against human Complement factor I	Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2’-(methylsulfonyl)-[1,1’-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa. — *J Med Chem*

Cellosaurus cell lines

19 cell lines: 17 induced pluripotent stem cell, 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2YF	SCTCi011-A	Induced pluripotent stem cell	Female
CVCL_A2YG	SCTCi012-A	Induced pluripotent stem cell	Male
CVCL_A2YH	SCTCi013-A	Induced pluripotent stem cell	Male
CVCL_B2MC	Abcam A-549 CFH KO	Cancer cell line	Male
CVCL_B4IK	iChEC-1	Transformed cell line	Female
CVCL_IT85	UNEWi022-A	Induced pluripotent stem cell	Male
CVCL_IT86	UNEWi022-B	Induced pluripotent stem cell	Male
CVCL_IT87	UNEWi022-C	Induced pluripotent stem cell	Male
CVCL_IT91	UNEWi024-A	Induced pluripotent stem cell	Male
CVCL_IT92	UNEWi024-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 314 trials:

NCT	Phase	Status	Title
NCT02574403	Phase 4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	Phase 4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT00067990	Phase 4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	Phase 4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	Phase 4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	Phase 4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	Phase 4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	Phase 4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	Phase 4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	Phase 4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	Phase 4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	Phase 4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	Phase 4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	Phase 4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	Phase 4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	Phase 4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	Phase 4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	Phase 4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	Phase 4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	Phase 4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	Phase 4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	Phase 4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	Phase 4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	Phase 4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	Phase 4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	Phase 4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	Phase 4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	Phase 4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	Phase 4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	Phase 4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	Phase 4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	Phase 4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	Phase 4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	Phase 4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	Phase 4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	Phase 4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	Phase 4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	Phase 4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	Phase 4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	Phase 4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	Phase 4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
NCT03160729	Phase 4	TERMINATED	High vs Low Dose Dexamethasone on Complications in the Immediate Postoperative Phase After Nephrectomy
NCT03387826	Phase 4	COMPLETED	Low Dose Ticagrelor Versus Low Dose Prasugrel in Patients With Prior Myocardial Infarction
NCT03623568	Phase 4	WITHDRAWN	Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant
NCT04080076	Phase 4	WITHDRAWN	Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy
NCT04539418	Phase 4	COMPLETED	Vitamin K2 Supplementation and Vascular Calcification
NCT04653779	Phase 4	UNKNOWN	A Clinical Trial to Evaluate the Preference Regarding Convenience of Medication and Efficacy/Safety of SUGAMET®XR Tablet 5/1000mg
NCT04839536	Phase 4	UNKNOWN	Comparing Sevoflurane With Propofol Sedation in ESRF Patients
NCT05030974	Phase 4	COMPLETED	RECOVAC Repeated Vaccination Study
NCT05096195	Phase 4	ACTIVE_NOT_RECRUITING	PRevEnting FracturEs in REnal Disease - 1
NCT05700903	Phase 4	TERMINATED	Contributions to Hypertension With Androgen Deprivation Therapy
NCT06291077	Phase 4	RECRUITING	Comparison of the Effects of Belatacept and Anticalcineurins on Endothelial Function in Renal Transplant Patients -
NCT06625073	Phase 4	RECRUITING	Randomized Trial of SGLT2i in Heart Transplant Recipients
NCT06642623	Phase 4	RECRUITING	A Prospective Trial of Enavogliflozin to Evaluate Cardio-renal Outcome in Type 2 Diabetes Mellitus Patients
NCT07138521	Phase 4	NOT_YET_RECRUITING	Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation
NCT07182422	Phase 4	RECRUITING	AST-120 (Kremezin®) for the Renal Protection and Attenuation of Decline in Acute Kidney Disease
NCT07685886	Phase 4	NOT_YET_RECRUITING	MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes
NCT07746219	Phase 4	NOT_YET_RECRUITING	The Clinical Research of Traditional Chinese Medicine Formula
NCT05067127	Phase 3	COMPLETED	Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CFH across ~30M SureChEMBL compounds — explore on Sugi Predict.