C8A

Summary

C8A (complement C8 alpha chain, HGNC:1352) is a protein-coding gene on chromosome 1p32.2, encoding Complement component C8 alpha chain (P07357). Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis.

C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency.

Source: NCBI Gene 731 — RefSeq curated summary.

At a glance

• Gene–disease (curated): type I complement component 8 deficiency (Strong, GenCC)
• Clinical variants (ClinVar): 457 total — 21 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_000562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1352
Approved symbol	C8A
Name	complement C8 alpha chain
Location	1p32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157131
Ensembl biotype	protein_coding
OMIM	120950
Entrez	731

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 13 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay, 1 non_stop_decay

ENST00000361249, ENST00000695676, ENST00000695677, ENST00000695678, ENST00000695679, ENST00000695680, ENST00000695681, ENST00000695682, ENST00000695683, ENST00000695684, ENST00000695685, ENST00000695686, ENST00000695687, ENST00000695688, ENST00000695723, ENST00000854262, ENST00000854263, ENST00000854264, ENST00000854265, ENST00000854266, ENST00000854267, ENST00000854268, ENST00000854269, ENST00000854270

RefSeq mRNA: 1 — MANE Select: NM_000562 NM_000562

CCDS: CCDS606

Canonical transcript exons

ENST00000361249 — 11 exons

Exon	Start	End
ENSE00001381670	56881445	56881634
ENSE00001436552	56885927	56886167
ENSE00003964697	56854797	56854978
ENSE00003964705	56912403	56912625
ENSE00003964707	56907956	56908113
ENSE00003964710	56883481	56883681
ENSE00003964713	56867609	56867702
ENSE00003964716	56917565	56918223
ENSE00003964719	56876062	56876209
ENSE00003964721	56874949	56875093
ENSE00003964829	56906667	56906792

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 98.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.6393 / max 1175.4956, expressed in 28 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2997	1.7452	24
2998	0.4470	11
2999	0.4061	13
201522	0.0410	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.95	gold quality
liver	UBERON:0002107	98.59	gold quality
buccal mucosa cell	CL:0002336	83.73	gold quality
endometrium epithelium	UBERON:0004811	71.73	gold quality
gall bladder	UBERON:0002110	70.36	gold quality
tongue squamous epithelium	UBERON:0006919	63.96	gold quality
olfactory bulb	UBERON:0002264	62.07	gold quality
diaphragm	UBERON:0001103	60.24	gold quality
frontal pole	UBERON:0002795	59.69	gold quality
nasal cavity epithelium	UBERON:0005384	59.65	gold quality
middle frontal gyrus	UBERON:0002702	59.57	gold quality
oocyte	CL:0000023	59.28	gold quality
paraflocculus	UBERON:0005351	59.28	gold quality
duodenum	UBERON:0002114	57.65	gold quality
decidua	UBERON:0002450	56.55	gold quality
myocardium	UBERON:0002349	56.08	gold quality
inferior olivary complex	UBERON:0002127	55.09	gold quality
pancreatic ductal cell	CL:0002079	55.00	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	54.53	gold quality
jejunal mucosa	UBERON:0000399	53.84	silver quality
vastus lateralis	UBERON:0001379	53.52	gold quality
quadriceps femoris	UBERON:0001377	53.48	gold quality
hair follicle	UBERON:0002073	53.32	gold quality
tendon of biceps brachii	UBERON:0008188	53.29	gold quality
lower lobe of lung	UBERON:0008949	53.26	silver quality
epithelial cell of pancreas	CL:0000083	52.64	gold quality
cardia of stomach	UBERON:0001162	52.43	gold quality
cranial nerve II	UBERON:0000941	52.03	silver quality
heart right ventricle	UBERON:0002080	51.27	gold quality
substantia nigra pars compacta	UBERON:0001965	51.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.75
E-ENAD-17	no	53.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting C8A, 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-3162-3P	100.00	65.37	363
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-4445-5P	97.21	66.16	832
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-490-5P	96.75	65.81	661

Literature-anchored findings (GeneRIF, showing 10)

• The binding specificity between C8 alpha and C8 beta subunits is determined by a cooperative interaction of the N-terminal thrombospondin type 1 module and the membrane attack complex/perforin domain. (PMID:12220191)
• C8 alpha and C8 beta have correspondingly similar roles in MAC-mediated lysis of erythrocytes and bacterial killing. C8 gamma is not required for complement-mediated killing of Gram-negative bacteria. (PMID:12413696)
• Both N-terminal modules in C8 alpha have a role in forming the principal binding site for C9, and binding may be dependent on a cooperative interaction between these modules and the C8 alpha membrane attack complex/perforin domain. (PMID:12463754)
• result suggests that this segment of C8alpha and corresponding segments of the other MAC family members are independently folded domains (PMID:16618117)
• One can predict that the indel segment of C8alpha assumes a conformation that allows for multiple points of contact with C8gamma. (PMID:16935577)
• crystal structure of the MACPF domain of complement component C8alpha at 2.5 angstrom resolution was determined and it was shown that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins (PMID:17872444)
• Results describe the crystal structure of the human C8 alpha MACPF domain disulfide-linked to C8 gamma (alphaMACPF-gamma) at 2.15 A resolution. (PMID:18440555)
• C8gamma binds an indel peptide of C8alpha sequence and forms a non-covalent complex. (PMID:19048311)
• These data provide a detailed specification of co-occurring C8 proteoforms, including experimental evidence on N-glycosylation, C-mannosylation, and O-glycosylation. (PMID:29532326)
• A Point Mutation Creating a 3’ Splice Site in C8A Is a Predominant Cause of C8alpha-gamma Deficiency in African Americans. (PMID:32769119)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	C8a	ENSMUSG00000035031
rattus_norvegicus	C8a	ENSRNOG00000007697

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), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), 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 component C8 alpha chain — P07357 (reviewed: P07357)

Alternative names: Complement component 8 subunit alpha

All UniProt accessions (6): P07357, A0A8Q3WKN0, A0A8Q3WKN4, A0A8Q3WKQ2, A0A8Q3WKT7, A0A8Q3WL79

UniProt curated annotations — full annotation on UniProt →

Function. Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis. The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways. The complement pathways consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. C8A, together with C8B and C8G, inserts into the target membrane, but does not form pores by itself. During MAC assembly, associates with C5b, C6 and C7 to form the C5b8 intermediate complex that inserts into the target membrane and traverses the bilayer increasing membrane rigidity.

Subunit / interactions. Heterotrimer of 3 chains: alpha (C8A), beta (C8B) and gamma (C8G); the alpha and gamma chains are disulfide bonded. Component of the membrane attack complex (MAC), composed of complement C5b, C6, C7, C8A, C8B, C8G and multiple copies of the pore-forming subunit C9.

Subcellular location. Secreted. Target cell membrane.

Disease relevance. Complement component 8 deficiency, 1 (C8D1) [MIM:613790] A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Membrane attack complex (MAC) assembly is inhibited by CD59, thereby protecting self-cells from damage during complement activation. CD59 acts by binding to the beta-haipins of C8 (C8A and C8B), forming an intermolecular beta-sheet that prevents incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. MAC assembly is also inhibited by clusterin (CLU) chaperones that inhibit polymerization of C9.

Similarity. Belongs to the complement C6/C7/C8/C9 family.

RefSeq proteins (1): NP_000553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001862	MAC_perforin	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR020863	MACPF_CS	Conserved_site
IPR020864	MACPF	Domain
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR048831	C8A_B_C6_EGF-like	Domain

Pfam: PF00057, PF00090, PF01823, PF21195

UniProt features (104 total): strand 34, helix 16, disulfide bond 15, sequence variant 7, binding site 6, turn 6, domain 5, glycosylation site 5, transmembrane region 4, signal peptide 1, propeptide 1, region of interest 1, site 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2QOS	X-RAY DIFFRACTION	1.81
2RD7	X-RAY DIFFRACTION	2.15
2QQH	X-RAY DIFFRACTION	2.5
3OJY	X-RAY DIFFRACTION	2.51
8B0F	ELECTRON MICROSCOPY	3
7NYD	ELECTRON MICROSCOPY	3.27
8B0G	ELECTRON MICROSCOPY	3.3
8B0H	ELECTRON MICROSCOPY	3.3
7NYC	ELECTRON MICROSCOPY	3.54
6H03	ELECTRON MICROSCOPY	5.6
6H04	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07357-F1	79.58	0.32

Functional residue map

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

Catalytic / active sites (1): 43 (not glycosylated)

Ligand- & substrate-binding residues (6): 113; 116; 118; 120; 126; 127

Disulfide bonds (15): 39–74, 50–84, 53–90, 96–108, 102–121, 115–130, 140–177, 194, 375–399, 497–544, 499–515, 502–517, 519–528, 551–584, 562–574

Glycosylation sites (5): 44, 437, 542, 545, 548

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-166665	Terminal pathway of complement
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 139 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_GSTM1, GNF2_HPN, HNF1_Q6, CHX10_01, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_COMPLEMENT_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, KEGG_PRION_DISEASES, GOBP_COMPLEMENT_ACTIVATION_ALTERNATIVE_PATHWAY

GO Biological Process (10): immune response (GO:0006955), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), complement activation, classical pathway (GO:0006958), killing of cells of another organism (GO:0031640), positive regulation of immune response (GO:0050778), transmembrane transport (GO:0055085), complement activation, GZMK pathway (GO:0160257), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (3): complement binding (GO:0001848), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), membrane attack complex (GO:0005579), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), membrane (GO:0016020), other organism cell membrane (GO:0044218), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), transmembrane transporter complex (GO:1902495)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Complement cascade	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	3
cellular anatomical structure	3
innate immune response	2
immune response	2
binding	2
immune system process	1
response to stimulus	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
humoral immune response mediated by circulating immunoglobulin	1
cell killing	1
disruption of cell in another organism	1
positive regulation of immune system process	1
positive regulation of response to stimulus	1
regulation of immune response	1
transport	1
cellular process	1
biological_process	1
defense response to symbiont	1
protein binding	1
pore complex	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
other organism part	1
extracellular vesicle	1
extracellular region	1
membrane protein complex	1
transporter complex	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C8A	C8G	P07360	984
C8A	C5	P01031	909
C8A	C4A	P01028	907
C8A	C8B	P07358	836
C8A	C3	P01024	800
C8A	C4BPB	P20851	744
C8A	PGM1	P36871	649
C8A	HLA-DRB5	Q30154	640
C8A	C1S	P09871	639
C8A	C1R	P00736	598
C8A	VTN	P01141	578
C8A	C4BPA	P04003	571
C8A	CFHR1	Q03591	565
C8A	SERPINF2	P08697	563
C8A	ITIH1	P19827	559

IntAct

27 interactions, top by confidence:

A	B	Type	Score
C8A	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
C8A	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
C8A	GOLT1A	psi-mi:“MI:0915”(physical association)	0.560
C8A	MMGT1	psi-mi:“MI:0915”(physical association)	0.560
C8A	GPR152	psi-mi:“MI:0915”(physical association)	0.560
C5	C9	psi-mi:“MI:0915”(physical association)	0.550
C8A	IDE	psi-mi:“MI:0914”(association)	0.530
	C8A	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
RSPH4A	C8A	psi-mi:“MI:0915”(physical association)	0.400
MMP14	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CMIP	INPPL1	psi-mi:“MI:0914”(association)	0.350
C8A	HSPA5	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
	C5	psi-mi:“MI:0915”(physical association)	0.320
C8A	MMGT1	psi-mi:“MI:0915”(physical association)	0.000
C8A	GPR152	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): C8A (Two-hybrid), C8A (Two-hybrid), MMGT1 (Two-hybrid), GOLT1A (Two-hybrid), GPR152 (Two-hybrid), C8G (Reconstituted Complex), CD59 (Reconstituted Complex), HSPA5 (Affinity Capture-MS), C8A (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), C8A (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), C8A (Affinity Capture-MS), IDE (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS97, A1L314, D3YXF5, E7F0Z8, O75339, P02748, P06682, P06683, P07357, P07358, P10643, P10820, P35763, P48747, P48770, P51578, P55314, P79755, P98136, P98137, Q2KJC3, Q2M385, Q3MHN2, Q3V5L5, Q5RBP9, Q62930, Q64663, Q66K08, Q66S13, Q66S17, Q66S21, Q66S25, Q6UX71, Q765H6, Q8BG22, Q8BH35, Q8K182, Q8L612, Q8N2E2, Q90X85

Diamond homologs: A0A0F7YYX3, P06682, P07357, A2AJX4, A2ARV4, A2VEC9, A6QNY1, B3EWZ6, G3V928, O75197, O75581, O88572, P0DSP1, P34434, P35953, P98155, P98156, P98157, P98158, P98160, P98162, P98164, P98165, P98166, P98167, Q05793, Q07954, Q14114, Q2PC93, Q5HZW5, Q5VYJ5, Q700K0, Q8CG65, Q91VN0, Q91ZX7, Q924X6, Q98931, Q9NPF0, Q9NZR2, Q9Z1P5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
C8A	“form complex”	“Membrane attack complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	5
Uncertain significance	202
Likely benign	191
Benign	14

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1023205	NM_000562.3(C8A):c.1270C>T (p.Arg424Ter)	Pathogenic
1064346	NM_000562.3(C8A):c.213_219del (p.Thr72fs)	Pathogenic
1372154	NM_000562.3(C8A):c.456del (p.Ala153fs)	Pathogenic
1409664	NM_000562.3(C8A):c.175C>T (p.Arg59Ter)	Pathogenic
1426221	NM_000562.3(C8A):c.1396G>T (p.Glu466Ter)	Pathogenic
2102582	NM_000562.3(C8A):c.131G>A (p.Trp44Ter)	Pathogenic
2423328	NC_000001.10:g.(?57351580)(57351860_?)del	Pathogenic
2809688	NM_000562.3(C8A):c.1421_1422insCA (p.Pro475fs)	Pathogenic
2867575	NM_000562.3(C8A):c.1079del (p.Ala360fs)	Pathogenic
2905639	NM_000562.3(C8A):c.493C>T (p.Gln165Ter)	Pathogenic
2966773	NM_000562.3(C8A):c.565C>T (p.Arg189Ter)	Pathogenic
2968639	NM_000562.3(C8A):c.579del (p.Cys194fs)	Pathogenic
2999998	NM_000562.3(C8A):c.832G>T (p.Glu278Ter)	Pathogenic
3009370	NM_000562.3(C8A):c.1435A>T (p.Lys479Ter)	Pathogenic
3646846	NM_000562.3(C8A):c.975C>A (p.Tyr325Ter)	Pathogenic
3677358	NM_000562.3(C8A):c.420C>A (p.Cys140Ter)	Pathogenic
3687350	NM_000562.3(C8A):c.836T>G (p.Leu279Ter)	Pathogenic
3694359	NM_000562.3(C8A):c.554G>A (p.Trp185Ter)	Pathogenic
3713796	NM_000562.3(C8A):c.1147C>T (p.Gln383Ter)	Pathogenic
4696324	NM_000562.3(C8A):c.1346C>G (p.Ser449Ter)	Pathogenic
981205	GRCh37/hg19 1p32.3-31.3(chr1:53675707-66644963)x1	Pathogenic
1388499	NM_000562.3(C8A):c.655-2A>G	Likely pathogenic
1905123	NM_000562.3(C8A):c.172-2A>G	Likely pathogenic
1964665	NM_000562.3(C8A):c.856-1G>A	Likely pathogenic
2167895	NM_000562.3(C8A):c.1222+1G>A	Likely pathogenic
29660	NM_000562.3(C8A):c.171+1G>T	Likely pathogenic

SpliceAI

1702 predictions. Top by Δscore:

Variant	Effect	Δscore
1:56867603:CTTTA:C	acceptor_loss	1.0000
1:56867604:TTTA:T	acceptor_loss	1.0000
1:56867605:TTAG:T	acceptor_loss	1.0000
1:56867606:TA:T	acceptor_loss	1.0000
1:56867608:GGA:G	acceptor_gain	1.0000
1:56867608:GGAGA:G	acceptor_gain	1.0000
1:56867700:AAGG:A	donor_loss	1.0000
1:56867702:GGTGA:G	donor_loss	1.0000
1:56867703:GTG:G	donor_loss	1.0000
1:56867704:T:G	donor_loss	1.0000
1:56876167:GCCA:G	donor_gain	1.0000
1:56876171:G:GG	donor_gain	1.0000
1:56881619:G:GT	donor_gain	1.0000
1:56881632:GAA:G	donor_gain	1.0000
1:56881635:G:GG	donor_gain	1.0000
1:56883477:TCA:T	acceptor_loss	1.0000
1:56883478:CAGG:C	acceptor_loss	1.0000
1:56883479:A:AG	acceptor_gain	1.0000
1:56883479:AG:A	acceptor_gain	1.0000
1:56883480:G:GG	acceptor_gain	1.0000
1:56883480:GG:G	acceptor_gain	1.0000
1:56883480:GGC:G	acceptor_gain	1.0000
1:56883480:GGCC:G	acceptor_gain	1.0000
1:56883480:GGCCC:G	acceptor_gain	1.0000
1:56883615:GGGT:G	donor_gain	1.0000
1:56883616:GGT:G	donor_gain	1.0000
1:56883616:GGTG:G	donor_gain	1.0000
1:56883617:GT:G	donor_gain	1.0000
1:56883617:GTG:G	donor_gain	1.0000
1:56883618:TGT:T	donor_gain	1.0000

AlphaMissense

3863 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:56867672:G:C	W47C	0.996
1:56867672:G:T	W47C	0.996
1:56908071:G:C	W446C	0.996
1:56908071:G:T	W446C	0.996
1:56876106:T:A	C121S	0.995
1:56876107:G:C	C121S	0.995
1:56875081:T:A	C102S	0.994
1:56875082:G:C	C102S	0.994
1:56885966:G:C	A299P	0.994
1:56917596:G:C	W545C	0.994
1:56917596:G:T	W545C	0.994
1:56876088:T:A	C115S	0.992
1:56876089:G:C	C115S	0.992
1:56881535:G:C	W185C	0.992
1:56881535:G:T	W185C	0.992
1:56876108:C:G	C121W	0.990
1:56881613:C:A	N211K	0.990
1:56881613:C:G	N211K	0.990
1:56867663:G:C	W44C	0.989
1:56867663:G:T	W44C	0.989
1:56885973:T:C	F301S	0.989
1:56876106:T:C	C121R	0.988
1:56886113:G:T	G348C	0.988
1:56908069:T:A	W446R	0.988
1:56908069:T:C	W446R	0.988
1:56917587:G:C	W542C	0.988
1:56917587:G:T	W542C	0.988
1:56876107:G:A	C121Y	0.987
1:56876067:T:A	C108S	0.986
1:56876068:G:C	C108S	0.986

dbSNP variants (sampled 300 via entrez): RS1000093283 (1:56864431 T>C), RS1000130059 (1:56902798 C>T), RS1000134929 (1:56884086 A>T), RS1000168887 (1:56875515 G>T), RS1000188903 (1:56913594 C>T), RS1000214759 (1:56856817 A>T), RS1000230275 (1:56903045 C>T), RS1000245875 (1:56908178 C>A,T), RS1000321525 (1:56869758 G>C), RS1000328755 (1:56858680 G>T), RS1000390337 (1:56880934 T>G), RS1000398813 (1:56870139 T>G), RS1000400627 (1:56884370 G>A), RS1000452114 (1:56875251 C>A), RS1000549195 (1:56855566 G>A,T)

Disease associations

OMIM: gene MIM:120950 | disease phenotypes: MIM:613790

GenCC curated gene-disease

Disease	Classification	Inheritance
type I complement component 8 deficiency	Strong	Autosomal recessive

Mondo (2): type I complement component 8 deficiency (MONDO:0013422), chromosome 1p32-p31 deletion syndrome (MONDO:0013396)

Orphanet (1): 1p31p32 microdeletion syndrome (Orphanet:401986)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001287	Meningitis
HP:0002725	Systemic lupus erythematosus
HP:0004434	Decreased circulating complement C8 concentration

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, decreases expression, decreases methylation, increases methylation	5
Aflatoxin B1	decreases expression, affects expression	4
Cyclosporine	affects expression, decreases expression	3
bisphenol A	affects expression, decreases expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
periodate-oxidized adenosine	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
(+)-JQ1 compound	decreases expression	1
Rosiglitazone	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Methotrexate	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	affects binding	1
Quercetin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, decreases methylation	1
Zinc	affects binding	1

Clinical trials (associated diseases)

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