C8B

Summary

C8B (complement C8 beta chain, HGNC:1353) is a protein-coding gene on chromosome 1p32.2, encoding Complement component C8 beta chain (P07358). 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.

This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 732 — RefSeq curated summary.

At a glance

• Gene–disease (curated): type II complement component 8 deficiency (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 445 total — 32 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_000066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1353
Approved symbol	C8B
Name	complement C8 beta chain
Location	1p32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000021852
Ensembl biotype	protein_coding
OMIM	120960
Entrez	732

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron, 1 non_stop_decay

ENST00000371237, ENST00000465658, ENST00000468990, ENST00000494324, ENST00000695842, ENST00000695843, ENST00000696144, ENST00000696164, ENST00000696165, ENST00000696166, ENST00000875298, ENST00000875299, ENST00000875300, ENST00000875301, ENST00000875302, ENST00000875303, ENST00000875304, ENST00000875305

RefSeq mRNA: 3 — MANE Select: NM_000066 NM_000066, NM_001278543, NM_001278544

CCDS: CCDS30730

Canonical transcript exons

ENST00000371237 — 12 exons

Exon	Start	End
ENSE00000413866	56943696	56943824
ENSE00001935318	56965857	56966015
ENSE00001957639	56956769	56956910
ENSE00003599544	56960020	56960176
ENSE00003965185	56940849	56941012
ENSE00003965186	56954686	56954827
ENSE00003965187	56952048	56952180
ENSE00003965188	56933335	56933488
ENSE00003965190	56931810	56931878
ENSE00003965197	56929207	56929558
ENSE00003965198	56949555	56949752
ENSE00003965202	56945821	56946061

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 99.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7857 / max 1120.4310, expressed in 23 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12540	2.6576	23
201523	0.1281	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.22	gold quality
liver	UBERON:0002107	98.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.04	silver quality
gluteal muscle	UBERON:0002000	74.85	gold quality
triceps brachii	UBERON:0001509	74.83	gold quality
quadriceps femoris	UBERON:0001377	66.88	gold quality
vastus lateralis	UBERON:0001379	66.66	gold quality
oocyte	CL:0000023	65.62	gold quality
frontal pole	UBERON:0002795	65.58	gold quality
paraflocculus	UBERON:0005351	65.27	gold quality
endometrium epithelium	UBERON:0004811	65.20	gold quality
middle frontal gyrus	UBERON:0002702	65.05	gold quality
superficial temporal artery	UBERON:0001614	64.30	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.28	gold quality
biceps brachii	UBERON:0001507	63.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.31	gold quality
deltoid	UBERON:0001476	63.23	gold quality
heart right ventricle	UBERON:0002080	62.35	gold quality
epithelium of nasopharynx	UBERON:0001951	61.24	gold quality
olfactory bulb	UBERON:0002264	60.60	gold quality
type B pancreatic cell	CL:0000169	60.36	gold quality
nasal cavity epithelium	UBERON:0005384	59.65	gold quality
lung	UBERON:0002048	59.36	gold quality
upper lobe of left lung	UBERON:0008952	59.26	gold quality
pancreatic ductal cell	CL:0002079	59.13	silver quality
gall bladder	UBERON:0002110	57.80	gold quality
upper lobe of lung	UBERON:0008948	57.52	gold quality
tibialis anterior	UBERON:0001385	57.27	silver quality
right lung	UBERON:0002167	56.92	gold quality
cerebellar vermis	UBERON:0004720	55.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting C8B, 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-4487	99.96	64.58	1252
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-1226-5P	96.50	65.28	643

Literature-anchored findings (GeneRIF, showing 6)

• The binding specificity between C8 beta and C8 alpha 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)
• results indicate that the principal binding site for C9 lies within the MACPF domain of C8alpha; they also suggest this site and the binding sites for C8beta and C8gamma are distinct (PMID:16618117)
• Cell cycle induction by C5b-9 in aortic endothelial cells is RGC-32 dependent and this is in part through regulation of Akt and growth factor release. (PMID:19162005)
• Complement C5b-9 induce a JNK/Bid-dependent and JNK-independent necrotic cell death. (PMID:19864026)
• These data provide a detailed specification of co-occurring C8 proteoforms, including experimental evidence on N-glycosylation, C-mannosylation, and O-glycosylation. (PMID:29532326)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c8b	ENSDARG00000039517
mus_musculus	C8b	ENSMUSG00000029656
rattus_norvegicus	C8b	ENSRNOG00000007639

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), 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)

Protein

Protein identifiers

Complement component C8 beta chain — P07358 (reviewed: P07358)

Alternative names: Complement component 8 subunit beta

All UniProt accessions (6): A0A8Q3SI88, A0A8Q3SIA7, A0A8Q3SJ17, P07358, A0A8Q3WL56, A0A8Q3WM97

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. C8B, together with C8A 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.

Post-translational modifications. N-glycosylated; contains one or two bound glycans. Not O-glycosylated.

Disease relevance. Complement component 8 deficiency, 2 (C8D2) [MIM:613789] 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.

Polymorphism. The sequence shown is that of allotype C8B A.

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

RefSeq proteins (3): NP_000057, NP_001265472, NP_001265473 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001862	MAC_perforin	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
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 (99 total): strand 26, helix 16, disulfide bond 13, turn 11, sequence variant 7, binding site 6, glycosylation site 6, domain 5, transmembrane region 4, signal peptide 1, propeptide 1, region of interest 1, modified residue 1, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
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-P07358-F1	81.99	0.49

Functional residue map

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

Ligand- & substrate-binding residues (6): 138; 141; 143; 145; 151; 152

Post-translational modifications (1): 418

Disulfide bonds (13): 65–100, 76–110, 79–116, 122–133, 127–146, 140–155, 162–200, 378–403, 503–550, 505–521, 508–523, 525–534, 557–590

Glycosylation sites (6): 70, 73, 101, 243, 551, 554

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: 116 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, HNF3ALPHA_Q6, GNF2_HPN, MODULE_16, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_COMPLEMENT_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, TGCTGAY_UNKNOWN, 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 (2): 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), extracellular vesicle (GO:1903561), 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
innate immune response	2
immune response	2
binding	2
cellular anatomical structure	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
pore complex	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
other organism part	1
extracellular vesicle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1
membrane protein complex	1
transporter complex	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C8B	C8G	P07360	980
C8B	C8A	P07357	836
C8B	C4A	P01028	785
C8B	C3	P01024	710
C8B	PGM1	P36871	697
C8B	C5	P01031	671
C8B	C1R	P00736	664
C8B	CD59	P13987	618
C8B	C1S	P09871	584
C8B	C4BPB	P20851	567
C8B	PGM2	Q96G03	550
C8B	C4A	P01028	513
C8B	C4BPA	P04003	507
C8B	HLA-DRB5	Q30154	495
C8B	CFB	P00751	490

IntAct

6 interactions, top by confidence:

A	B	Type	Score
C5	C9	psi-mi:“MI:0915”(physical association)	0.550
	C8A	psi-mi:“MI:0915”(physical association)	0.400
C8B	PAPSS2	psi-mi:“MI:0914”(association)	0.350
	C5	psi-mi:“MI:0915”(physical association)	0.320

BioGRID (8): C8B (Reconstituted Complex), C8B (Reconstituted Complex), PAPSS2 (Affinity Capture-MS), KDM1B (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), HHIPL1 (Affinity Capture-MS), C8A (Cross-Linking-MS (XL-MS)), C8B (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: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
C8B	“form complex”	“Membrane attack complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	8
Uncertain significance	210
Likely benign	157
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032165	NM_000066.4(C8B):c.27G>A (p.Trp9Ter)	Pathogenic
1073946	NC_000001.10:g.(?57417701)(57417873_?)del	Pathogenic
1325387	NM_000066.4(C8B):c.348C>A (p.Cys116Ter)	Pathogenic
1375292	NM_000066.4(C8B):c.934dup (p.Met312fs)	Pathogenic
1448095	NM_000066.4(C8B):c.1351G>T (p.Glu451Ter)	Pathogenic
1450812	NM_000066.4(C8B):c.1355G>A (p.Trp452Ter)	Pathogenic
1453039	NM_000066.4(C8B):c.739A>T (p.Lys247Ter)	Pathogenic
1453762	NM_000066.4(C8B):c.550_553del (p.Asn184fs)	Pathogenic
1457268	NM_000066.4(C8B):c.355C>T (p.Gln119Ter)	Pathogenic
1457326	NM_000066.4(C8B):c.793G>T (p.Glu265Ter)	Pathogenic
1457390	NM_000066.4(C8B):c.53del (p.Leu18fs)	Pathogenic
17038	NM_000066.4(C8B):c.1282C>T (p.Arg428Ter)	Pathogenic
1959060	NM_000066.4(C8B):c.71_74del (p.Cys24fs)	Pathogenic
2014711	NM_000066.4(C8B):c.667del (p.Thr223fs)	Pathogenic
2080806	NM_000066.4(C8B):c.210G>A (p.Trp70Ter)	Pathogenic
2103578	NM_000066.4(C8B):c.1115_1116del (p.Leu372fs)	Pathogenic
2184961	NM_000066.4(C8B):c.850C>T (p.Arg284Ter)	Pathogenic
2693317	NM_000066.4(C8B):c.1093dup (p.Met365fs)	Pathogenic
2697996	NM_000066.4(C8B):c.197del (p.Glu66fs)	Pathogenic
2747900	NM_000066.4(C8B):c.1142dup (p.Asn381fs)	Pathogenic
2789944	NM_000066.4(C8B):c.478A>T (p.Lys160Ter)	Pathogenic
2844283	NM_000066.4(C8B):c.477T>G (p.Tyr159Ter)	Pathogenic
2857921	NM_000066.4(C8B):c.493G>T (p.Glu165Ter)	Pathogenic
2865963	NM_000066.4(C8B):c.742del (p.Met248fs)	Pathogenic
2955240	NM_000066.4(C8B):c.1441del (p.Tyr481fs)	Pathogenic
35592	NM_000066.4(C8B):c.820C>T (p.Arg274Ter)	Pathogenic
35595	NM_000066.4(C8B):c.336del (p.Asn113fs)	Pathogenic
35596	NM_000066.4(C8B):c.605del (p.Pro202fs)	Pathogenic
35597	NM_000066.4(C8B):c.1041_1047dup (p.Leu350fs)	Pathogenic
3648337	NM_000066.4(C8B):c.149_153del (p.Ser50fs)	Pathogenic

SpliceAI

1659 predictions. Top by Δscore:

Variant	Effect	Δscore
1:56931808:A:AC	donor_gain	1.0000
1:56931809:C:CC	donor_gain	1.0000
1:56931809:CT:C	donor_gain	1.0000
1:56931809:CTCTT:C	donor_gain	1.0000
1:56931878:CCTG:C	acceptor_loss	1.0000
1:56933357:T:A	donor_gain	1.0000
1:56933391:T:TA	donor_gain	1.0000
1:56940853:A:C	donor_gain	1.0000
1:56949549:ACT:A	donor_loss	1.0000
1:56949551:TT:T	donor_loss	1.0000
1:56949552:TA:T	donor_loss	1.0000
1:56949553:A:AC	donor_gain	1.0000
1:56949553:A:T	donor_loss	1.0000
1:56949554:C:CG	donor_gain	1.0000
1:56949554:CA:C	donor_gain	1.0000
1:56949554:CAG:C	donor_gain	1.0000
1:56949554:CAGT:C	donor_gain	1.0000
1:56949554:CAGTA:C	donor_gain	1.0000
1:56949753:C:CC	acceptor_gain	1.0000
1:56929556:TATC:T	acceptor_loss	0.9900
1:56929557:ATCT:A	acceptor_loss	0.9900
1:56929558:TC:T	acceptor_loss	0.9900
1:56929560:T:C	acceptor_loss	0.9900
1:56931803:AACTT:A	donor_loss	0.9900
1:56931804:A:C	donor_gain	0.9900
1:56931804:ACTTA:A	donor_loss	0.9900
1:56931805:CTTAC:C	donor_loss	0.9900
1:56931806:TTA:T	donor_loss	0.9900
1:56931807:TACTC:T	donor_loss	0.9900
1:56931874:TGATC:T	acceptor_gain	0.9900

AlphaMissense

3908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:56954800:C:G	C140S	0.996
1:56954801:A:T	C140S	0.996
1:56954782:C:G	C146S	0.995
1:56954783:A:T	C146S	0.995
1:56940891:C:A	W452C	0.994
1:56940891:C:G	W452C	0.994
1:56960050:C:A	W73C	0.994
1:56960050:C:G	W73C	0.994
1:56954782:C:T	C146Y	0.993
1:56929536:C:A	W548C	0.992
1:56929536:C:G	W548C	0.992
1:56954781:A:C	C146W	0.992
1:56929527:C:A	W551C	0.991
1:56929527:C:G	W551C	0.991
1:56940893:A:G	W452R	0.991
1:56940893:A:T	W452R	0.991
1:56954783:A:G	C146R	0.991
1:56954821:C:G	C133S	0.991
1:56954822:A:T	C133S	0.991
1:56954782:C:A	C146F	0.990
1:56954801:A:G	C140R	0.989
1:56956779:A:C	C127W	0.989
1:56956780:C:G	C127S	0.989
1:56956781:A:T	C127S	0.989
1:56952069:A:C	N215K	0.988
1:56952069:A:T	N215K	0.988
1:56956780:C:T	C127Y	0.987
1:56956781:A:G	C127R	0.987
1:56956786:A:C	F125C	0.987
1:56956795:C:G	C122S	0.987

dbSNP variants (sampled 300 via entrez): RS1000004521 (1:56961743 C>G), RS1000028053 (1:56946219 C>A,G,T), RS1000091286 (1:56936790 A>G), RS1000132413 (1:56966775 A>G), RS1000134669 (1:56940907 T>C), RS1000158849 (1:56952084 A>C), RS1000213078 (1:56952301 C>G,T), RS1000255209 (1:56933171 G>A), RS1000309099 (1:56933941 A>G), RS1000315675 (1:56960689 C>A,G,T), RS1000370309 (1:56932921 C>G), RS1000436311 (1:56957490 G>A), RS1000609338 (1:56963156 A>G), RS1000695635 (1:56938452 G>T), RS1000733311 (1:56929768 C>T)

Disease associations

OMIM: gene MIM:120960 | disease phenotypes: MIM:613789, MIM:612446

GenCC curated gene-disease

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

Mondo (2): type II complement component 8 deficiency (MONDO:0013421), complement component 6 deficiency (MONDO:0012908)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001287	Meningitis
HP:0004434	Decreased circulating complement C8 concentration
HP:0005430	Recurrent Neisserial infections

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007006_1	Logical memory (delayed recall) in normal cognition	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects expression, decreases expression, increases expression	4
Aflatoxin B1	decreases expression, decreases methylation, affects expression	3
Benzo(a)pyrene	decreases expression, increases methylation	2
methyleugenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
K 7174	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Rosiglitazone	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Copper	affects binding	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	affects binding	1
Phthalic Acids	decreases methylation	1
Quercetin	decreases expression	1
Valproic Acid	decreases expression	1
Zinc	affects binding	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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