CFHR3

Summary

CFHR3 (complement factor H related 3, HGNC:16980) is a protein-coding gene on chromosome 1q31.3, encoding Complement factor H-related protein 3 (Q02985). Might be involved in complement regulation.

The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10878 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic uremic syndrome, atypical, susceptibility to, 1 (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 126 total — 1 pathogenic
• Phenotypes (HPO): 33
• MANE Select transcript: NM_021023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16980
Approved symbol	CFHR3
Name	complement factor H related 3
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FHR-3, HLF4, FHR3, DOWN16
Ensembl gene	ENSG00000116785
Ensembl biotype	protein_coding
OMIM	605336
Entrez	10878

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000367425, ENST00000367427, ENST00000391985, ENST00000461558, ENST00000471440, ENST00000907750, ENST00000907751, ENST00000907752, ENST00000907753, ENST00000907754, ENST00000907755, ENST00000907756, ENST00000907757

RefSeq mRNA: 2 — MANE Select: NM_021023 NM_001166624, NM_021023

CCDS: CCDS30958, CCDS53453

Canonical transcript exons

ENST00000367425 — 6 exons

Exon	Start	End
ENSE00001444482	196774840	196774944
ENSE00001913740	196793317	196795407
ENSE00002327094	196779162	196779356
ENSE00002369762	196779797	196779973
ENSE00002383799	196788216	196788398
ENSE00003461839	196790045	196790227

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1449 / max 93.2164, expressed in 7 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7507	0.1192	7
7506	0.0140	5
7505	0.0117	4

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.05	gold quality
liver	UBERON:0002107	95.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.24	gold quality
metanephric glomerulus	UBERON:0004736	79.29	gold quality
endometrium epithelium	UBERON:0004811	62.18	gold quality
frontal pole	UBERON:0002795	61.68	gold quality
middle frontal gyrus	UBERON:0002702	61.64	gold quality
paraflocculus	UBERON:0005351	61.23	gold quality
colonic epithelium	UBERON:0000397	60.69	silver quality
cerebellar vermis	UBERON:0004720	60.19	gold quality
left coronary artery	UBERON:0001626	59.88	gold quality
coronary artery	UBERON:0001621	58.68	gold quality
right coronary artery	UBERON:0001625	58.26	gold quality
popliteal artery	UBERON:0002250	57.74	gold quality
tibial artery	UBERON:0007610	57.73	gold quality
tibial nerve	UBERON:0001323	57.47	gold quality
descending thoracic aorta	UBERON:0002345	56.67	gold quality
right atrium auricular region	UBERON:0006631	56.43	gold quality
cardiac atrium	UBERON:0002081	56.01	gold quality
aorta	UBERON:0000947	56.00	gold quality
lower lobe of lung	UBERON:0008949	55.73	silver quality
gall bladder	UBERON:0002110	55.39	gold quality
left ovary	UBERON:0002119	54.67	gold quality
thoracic aorta	UBERON:0001515	53.90	gold quality
ascending aorta	UBERON:0001496	53.74	gold quality
right lung	UBERON:0002167	53.27	gold quality
lymph node	UBERON:0000029	52.42	gold quality
ovary	UBERON:0000992	52.20	gold quality
Brodmann (1909) area 10	UBERON:0013541	52.19	gold quality
thymus	UBERON:0002370	51.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	224.93
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting CFHR3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517

Literature-anchored findings (GeneRIF, showing 40)

• First detailed description of structure of human FHR3 gene (PMID:10781834)
• A common haplotype was associated with decreased risk of AMD. This haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. (PMID:16998489)
• Deletion of two closely related genes, complement factor H-related 1 (CFHR1) and complement factor H-related 3 (CFHR3), increases the risk of atypical hemolytic uremic syndrome. (PMID:17367211)
• either lacked the CFHR1/CFHR3 completely (n = 14) or showed extremely low CFHR1/CFHR3 plasma levels (n = 2) are positive for factor H (CFH) autoantibodies (PMID:18006700)
• deletion of CFHR1 and CFHR3 may account for a small portion of the protection from age-related macular degeneration associated with particular haplotypes in complement factor H. (PMID:18084039)
• Results describe a correlation between the development of complement factor H autoantibodies and the deficiency of the CFH-related proteins, CFHR1 and CFHR3, in atypical hemolytic uremic syndrome. (PMID:19531976)
• Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. (PMID:19553609)
• Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. (PMID:19861685)
• Data from haplotype analysis demonstrates the relationship between the CFH rs10737680 association and the CFHR1-3Delta association in age-related macular degeneration. (PMID:20581873)
• deficiency of CFHR3 and CFHR1 results in a loss of complement control but enhances local regulation by factor H; alludes to critical balance between CFHR3, CFHR1 and factor H and emphasize role of complement regulation in age-related macular degeneration (PMID:20843825)
• A change in gene dosage of the encoded proteins CFHR3 and CFHR1 might account for the increased systemic lupus erythematosus. (PMID:21637784)
• Data show that 698 CNPs loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3, CFHR1, GSTTI and UGT2B17. (PMID:21677662)
• Combined deletion of CFHR3 and CFHR1is associated with a decreased risk of developing age-related macular degeneration. (PMID:21850184)
• In this matched subset of Age-Related Eye Disease Study (AREDS) subjects, after adjusting for 2 known risk variants in CFH, CNP147 deletion statistically associates with diminished risk for AMD. (PMID:21856016)
• A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion is associated with familial atypical hemolytic uremic syndrome. (PMID:22058112)
• Significant association was identified for the CFHR3-1 deletion in age-related macular degeneration cases, for both neovascular disease and geographic atrophy. (PMID:22558131)
• A hybrid CFHR3-1 gene causes familial C3 glomerulopathy. (PMID:22626820)
• genetic variations in CFH and its related genes may contribute to hypertension risk in Chinese Hans (PMID:22848687)
• Prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS. (PMID:24088957)
• Atypical haemolytic-uraemic syndrome due to heterozygous mutations of CFH/CFHR1-3 and complement factor H 479. (PMID:24333077)
• we have assessed the relationship between GA and previously identified AMD-associated variants of genes (CFH, CFB, C3, FHR1, FRH3, and ARMS2/HTRA). (PMID:24557084)
• Genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby predispose patients to develop IgA nephropathy. (PMID:25205734)
• Studies indicate that complement factor H-related proteins (FHR1-5) may enhance complement activation, with important implications for the role of these proteins in disease. (PMID:25979655)
• These results suggest that the combination of quantitative and qualitative variations in the complement proteins encoded by CFH, CFHR3 and CFHR1 genes is key for the association of these haplotypes with disease. (PMID:26163426)
• We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology-mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation (PMID:26490391)
• Exploratory analyses of clinical and histopathologic parameters using the Oxford classification criteria revealed a suggestive association of CFHR3,1Delta with reduced tubulointerstitial injury. These data indicate that dysregulated activity of the alternative complement pathway contributes to IgAN pathogenesis in both Asians and Europeans and implicate CFHR3,1Delta as the functional allele at this locus (PMID:26940089)
• To our knowledge, this is the first evaluation of the involvement of the CFHR3/CFHR1 deletion and age-related macular degeneration in CFH Y402H polymorphism Brazilian patients. (PMID:26942649)
• Next-generation sequencing of the CFH region identified putatively functional variants (missense, splice site and indel) on the four common haplotypes. We found no expression of any of the five CFH-related genes in the retina or RPE/Choroid/Sclera, in contrast to the liver, which is the main source of the circulating proteins.[CFHR3] (PMID:27196323)
• These data provide evidence that FHR3, which is absent in patients with the autoimmune form of hemolytic uremic syndrome, is involved in B cell regulation (PMID:27279373)
• We conclude that the relationship between complement-regulatory proteins CFHR1 and CFHR3 and response to anti-CD20 mAb therapy varies based on the specific anti-CD20 mAb used. (PMID:27528699)
• In conclusion, the CFHR3,1D genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits. (PMID:29114042)
• These data suggest that increased plasma levels of FHR-3, altering the balance between factor H (FH) and FHR-3, likely impact the FH regulatory functions and contribute to the development of atypical hemolytic-uremic syndrome . (PMID:29740447)
• Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection. (PMID:31349540)
• Overexpression of CFHR3 suppressed proliferation and promoted apoptosis of HCC cells by inhibiting the PI3K/Akt/mTOR signaling pathway. (PMID:31524260)
• CFHR3 is a potential novel biomarker for hepatocellular carcinoma. (PMID:31709629)
• These findings provide a mechanistic explanation as to why the deletion of CFHR3 and CFHR1 is protective in AMD and highlight the importance of genetic variants within the CFH/CFHR3/CFHR1 locus in the recognition of altered-self in tissue homeostasis. (PMID:32321835)
• High prevalence of CFHR deletions in Indian women with pregnancy-associated hemolytic uremic syndrome. (PMID:34796567)
• Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells. (PMID:34819935)
• The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma. (PMID:35852862)
• Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations. (PMID:36007525)

Cross-species orthologs

0 orthologs

Paralogs (39): CFH (ENSG00000000971), 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), 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)

Protein

Protein identifiers

Complement factor H-related protein 3 — Q02985 (reviewed: Q02985)

Alternative names: DOWN16, H factor-like protein 3

All UniProt accessions (2): Q02985, Q6NSD3

UniProt curated annotations — full annotation on UniProt →

Function. Might be involved in complement regulation.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Disease relevance. 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. A deletion encompassing CFHR1 and CFHR3 is associated with an increased risk of atypical hemolytic uremic syndrome, likely due to a defective regulation of complement activation. Some patients carrying the deletion have serum anti-CFH autoantibodies.

Isoforms (2)

UniProt ID	Names	Canonical?
Q02985-1	1	yes
Q02985-2	2

RefSeq proteins (2): NP_001160096, NP_066303* (*=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 (29 total): disulfide bond 10, sequence conflict 6, domain 5, glycosylation site 4, signal peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02985-F1	91.93	0.84

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 (10): 23–72, 55–83, 87–129, 114–140, 146–192, 175–203, 210–253, 239–264, 268–319, 302–329

Glycosylation sites (4): 309, 108, 185, 205

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 126 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION, GOBP_HUMORAL_IMMUNE_RESPONSE, AACTTT_UNKNOWN, GOBP_IMMUNE_EFFECTOR_PROCESS, GOCC_BLOOD_MICROPARTICLE, GOMF_COMPLEMENT_BINDING, MODULE_23, GOMF_OPSONIN_BINDING, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_UP, REACTOME_COMPLEMENT_CASCADE, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, HIRSCH_CELLULAR_TRANSFORMATION_SIGNATURE_UP

GO Biological Process (1): complement activation (GO:0006956)

GO Molecular Function (2): complement component C3b binding (GO:0001851), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Complement cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
opsonin binding	1
complement binding	1
binding	1
extracellular vesicle	1
extracellular region	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFHR3	C3	P01024	963
CFHR3	CFB	P00751	892
CFHR3	ADAMTS13	Q76LX8	824
CFHR3	RBMS2	Q15434	808
CFHR3	MYBPH	Q13203	787
CFHR3	CFI	P05156	777
CFHR3	DGKE	P52429	772
CFHR3	C2	P06681	758
CFHR3	CD46	P15529	720
CFHR3	C4BPB	P20851	706
CFHR3	C4BPA	P04003	666
CFHR3	ARMS2	P0C7Q2	624
CFHR3	CD55	P08174	621
CFHR3	THBD	P07204	608
CFHR3	C4A	P01028	603

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CRP	CFHR3	psi-mi:“MI:0407”(direct interaction)	0.620
CFHR3	CFH	psi-mi:“MI:0915”(physical association)	0.400
CFHR3	PRKCA	psi-mi:“MI:0915”(physical association)	0.400
PRDX4	CFHR3	psi-mi:“MI:0915”(physical association)	0.370
CFHR3	TPM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CFH (Affinity Capture-MS), TPM2 (Affinity Capture-MS), C3 (Reconstituted Complex), CFH (Affinity Capture-MS), PRKCA (Affinity Capture-MS), PRDX4 (Two-hybrid)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P06909, P08174, P08603, P08607, P15529, P16109, P17690, P19070, P20023, P26644, P33703, P36980, P42201, P49457, P70105, P79138, P98109, Q01339, Q02985, Q03472, Q03591, Q07968, Q22328, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476

Diamond homologs: P05160, P06909, P36980, Q01016, Q02985, Q07968, Q28066, Q2HRD4, Q63515, Q6AX42, Q9BXR6, O62837, P08174, P08603, P14650, P15529, P49457, P68638, P68639, P79138, Q03472, Q03591, Q26422, Q28085, Q53EL9, Q5R4D0, Q60401, Q09101, Q501P1, A0JNA2, P17927, P19070, P28175, Q29RN8, Q4LDE5, Q7TSK2, Q923L3, Q92496, Q2VPA4, Q7Z407

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	71
Likely benign	27
Benign	16

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4293094	NM_021023.6(CFHR3):c.613+3_613+6del	Pathogenic

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
1:196779159:A:AG	acceptor_gain	1.0000
1:196779159:AAGT:A	acceptor_gain	1.0000
1:196779160:A:G	acceptor_gain	1.0000
1:196779791:CCTTA:C	acceptor_loss	1.0000
1:196779792:CTTA:C	acceptor_loss	1.0000
1:196779793:TTAG:T	acceptor_loss	1.0000
1:196779794:TAG:T	acceptor_loss	1.0000
1:196779795:A:AT	acceptor_loss	1.0000
1:196779796:G:T	acceptor_loss	1.0000
1:196779818:T:TA	acceptor_gain	1.0000
1:196779970:GTCA:G	donor_gain	1.0000
1:196779971:TCA:T	donor_gain	1.0000
1:196779972:CAGTA:C	donor_loss	1.0000
1:196779973:AGTAA:A	donor_loss	1.0000
1:196779974:G:GG	donor_gain	1.0000
1:196779975:TAAG:T	donor_loss	1.0000
1:196779976:AAGTA:A	donor_loss	1.0000
1:196779977:AGTA:A	donor_loss	1.0000
1:196788394:CATTA:C	donor_gain	1.0000
1:196788395:ATTA:A	donor_gain	1.0000
1:196788397:TA:T	donor_gain	1.0000
1:196788399:G:GG	donor_gain	1.0000
1:196789624:A:AG	acceptor_gain	1.0000
1:196789631:AAAGC:A	acceptor_gain	1.0000
1:196789632:AAGC:A	acceptor_gain	1.0000
1:196775795:T:G	donor_gain	0.9900
1:196779781:ATT:A	acceptor_gain	0.9900
1:196779788:T:G	acceptor_gain	0.9900
1:196779795:A:AG	acceptor_gain	0.9900
1:196779795:AG:A	acceptor_gain	0.9900

AlphaMissense

2140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:196790205:G:C	W258C	0.997
1:196790205:G:T	W258C	0.997
1:196779334:G:C	W77C	0.996
1:196779334:G:T	W77C	0.996
1:196779945:G:C	W134C	0.994
1:196779945:G:T	W134C	0.994
1:196788376:G:C	W197C	0.993
1:196788376:G:T	W197C	0.993
1:196790203:T:A	W258R	0.992
1:196790203:T:C	W258R	0.992
1:196779317:T:A	C72S	0.991
1:196779318:G:C	C72S	0.991
1:196788308:T:A	C175S	0.991
1:196788309:G:C	C175S	0.991
1:196790221:T:A	C264S	0.991
1:196790222:G:C	C264S	0.991
1:196793424:T:A	C302S	0.990
1:196793425:G:C	C302S	0.990
1:196779332:T:A	W77R	0.989
1:196779332:T:C	W77R	0.989
1:196779266:T:A	C55S	0.988
1:196779267:G:C	C55S	0.988
1:196779928:T:A	C129S	0.988
1:196779929:G:C	C129S	0.988
1:196790146:T:A	C239S	0.988
1:196790147:G:C	C239S	0.988
1:196779350:T:A	C83S	0.987
1:196779351:G:C	C83S	0.987
1:196779961:T:A	C140S	0.986
1:196779962:G:C	C140S	0.986

dbSNP variants (sampled 300 via entrez): RS1000360351 (1:196783724 A>G), RS1000370438 (1:196784281 C>T), RS1000531860 (1:196792729 A>G), RS1000605019 (1:196786923 A>G), RS1001296776 (1:196787104 C>A,T), RS1001482371 (1:196783019 T>C), RS1001595157 (1:196782803 C>G), RS1002026742 (1:196793931 T>C), RS1002106257 (1:196787929 A>G,T), RS1002946022 (1:196789199 T>A), RS1002948478 (1:196793129 T>C), RS1003160875 (1:196773573 G>A), RS1003275932 (1:196773214 T>C), RS1003945585 (1:196773048 G>A), RS1005082391 (1:196776491 C>A,T)

Disease associations

OMIM: gene MIM:605336 | disease phenotypes: MIM:235400, MIM:603075

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic uremic syndrome, atypical, susceptibility to, 1	Limited	Unknown

Mondo (4): hemolytic uremic syndrome, atypical, susceptibility to, 1 (MONDO:0009335), age related macular degeneration 1 (MONDO:0011285), kidney disorder (MONDO:0005240), atypical hemolytic-uremic syndrome (MONDO:0016244)

Orphanet (2): Atypical hemolytic uremic syndrome (Orphanet:2134), Shiga toxin-associated hemolytic uremic syndrome (Orphanet:90038)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000529	Progressive visual loss
HP:0000608	Macular degeneration
HP:0000822	Hypertension
HP:0000979	Purpura
HP:0001250	Seizure
HP:0001259	Coma
HP:0001269	Hemiparesis
HP:0001873	Thrombocytopenia
HP:0001919	Acute kidney injury
HP:0001923	Reticulocytosis
HP:0001937	Microangiopathic hemolytic anemia
HP:0001945	Fever
HP:0001981	Schistocytosis
HP:0002014	Diarrhea
HP:0002381	Aphasia
HP:0003077	Hyperlipidemia
HP:0003138	Increased blood urea nitrogen
HP:0003259	Elevated circulating creatinine concentration
HP:0003584	Late onset
HP:0005356	Decreased circulating complement factor I concentration
HP:0005369	Decreased circulating complement factor H concentration
HP:0005416	Decreased circulating complement factor B concentration
HP:0005421	Decreased circulating complement C3 concentration
HP:0005575	Hemolytic-uremic syndrome
HP:0011506	Choroidal neovascularization
HP:0012643	Foveal hypopigmentation
HP:0025574	Macular hemorrhage
HP:0030499	Macular drusen

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000762_1	Meningococcal disease	5.000000e-13
GCST001009_4	Nephropathy	3.000000e-10
GCST001679_9	Complement C3 and C4 levels	7.000000e-11
GCST001899_1	Age-related macular degeneration	1.000000e-16
GCST002655_15	IgA nephropathy	2.000000e-09
GCST002655_22	IgA nephropathy	7.000000e-07
GCST002655_5	IgA nephropathy	5.000000e-14
GCST003219_8	Advanced age-related macular degeneration	6.000000e-165
GCST90019044_2	Complement factor H-related protein 3 levels	1.000000e-27

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004983	complement C3 measurement
EFO:1001492	atrophic macular degeneration
EFO:0600056	complement factor H-related protein 3 measurement

MeSH disease descriptors (3)

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
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
C566411	Macular Degeneration, Age-Related, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	2
methyleugenol	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
JP8 aviation fuel	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Bosentan	affects expression	1
Air Pollutants	decreases expression	1
Camptothecin	increases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Endosulfan	affects cotreatment, decreases expression	1
Glycochenodeoxycholic Acid	decreases expression, affects cotreatment	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phenobarbital	affects expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1EU	Abcam A-549 CFHR3 KO 1	Cancer cell line	Male
CVCL_B2MD	Abcam A-549 CFHR3 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07403825	PHASE4	RECRUITING	Efficacy of Faricimab in Patients With Subretinal Hyper-reflective Material
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia