SUSD4

Summary

SUSD4 (sushi domain containing 4, HGNC:25470) is a protein-coding gene on chromosome 1q41, encoding Sushi domain-containing protein 4 (Q5VX71). Acts as a complement inhibitor by disrupting the formation of the classical C3 convertase.

Involved in negative regulation of complement activation, alternative pathway and negative regulation of complement activation, classical pathway. Predicted to be located in extracellular region and membrane. Predicted to be active in parallel fiber to Purkinje cell synapse and postsynaptic membrane.

Source: NCBI Gene 55061 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_017982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25470
Approved symbol	SUSD4
Name	sushi domain containing 4
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10052
Ensembl gene	ENSG00000143502
Ensembl biotype	protein_coding
OMIM	615827
Entrez	55061

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000342943, ENST00000343846, ENST00000344029, ENST00000366878, ENST00000470249, ENST00000484503, ENST00000484758, ENST00000494793, ENST00000497669, ENST00000608996, ENST00000679807, ENST00000679975, ENST00000680429, ENST00000681285, ENST00000681305, ENST00000681404, ENST00000681669, ENST00000873853, ENST00000873854, ENST00000873855, ENST00000948563

RefSeq mRNA: 3 — MANE Select: NM_017982 NM_001037175, NM_001410929, NM_017982

CCDS: CCDS31034, CCDS41471, CCDS91160

Canonical transcript exons

ENST00000366878 — 9 exons

Exon	Start	End
ENSE00001432918	223364057	223364176
ENSE00003703626	223363278	223363460
ENSE00003708281	223229197	223229388
ENSE00003709412	223268502	223268675
ENSE00003893978	223223249	223223631
ENSE00003895295	223220831	223222220
ENSE00003895413	223292439	223292651
ENSE00003895861	223264630	223264818
ENSE00003896105	223227594	223227738

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.30.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9443 / max 105.0423, expressed in 527 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17634	2.4496	487
17633	0.3440	178
17635	0.0882	55
17632	0.0625	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.30	gold quality
left ovary	UBERON:0002119	95.19	gold quality
esophagus mucosa	UBERON:0002469	94.66	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.02	gold quality
tongue squamous epithelium	UBERON:0006919	93.85	gold quality
gingival epithelium	UBERON:0001949	93.81	gold quality
nucleus accumbens	UBERON:0001882	93.66	gold quality
CA1 field of hippocampus	UBERON:0003881	93.10	gold quality
right ovary	UBERON:0002118	92.95	gold quality
gingiva	UBERON:0001828	92.49	gold quality
esophagus squamous epithelium	UBERON:0006920	92.46	gold quality
Ammon’s horn	UBERON:0001954	92.44	gold quality
hair follicle	UBERON:0002073	92.24	silver quality
squamous epithelium	UBERON:0006914	92.15	gold quality
epithelium of esophagus	UBERON:0001976	91.77	gold quality
islet of Langerhans	UBERON:0000006	91.46	gold quality
prefrontal cortex	UBERON:0000451	91.22	gold quality
anterior cingulate cortex	UBERON:0009835	90.92	gold quality
cingulate cortex	UBERON:0003027	90.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.65	gold quality
right frontal lobe	UBERON:0002810	90.57	gold quality
frontal cortex	UBERON:0001870	90.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.39	gold quality
ovary	UBERON:0000992	90.25	gold quality
pituitary gland	UBERON:0000007	90.19	gold quality
cerebral cortex	UBERON:0000956	90.15	gold quality
superior frontal gyrus	UBERON:0002661	89.98	gold quality
telencephalon	UBERON:0001893	89.89	gold quality
neocortex	UBERON:0001950	89.89	gold quality
adenohypophysis	UBERON:0002196	89.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	16.44
E-GEOD-81547	yes	10.72
E-ANND-3	yes	9.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting SUSD4, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119

Literature-anchored findings (GeneRIF, showing 5)

• analysis of cloning, expression, refolding, and tissue distribution of Sushi domain-containing protein 4 (PMID:20348246)
• Membrane-bound isoform SUSD4a inhibits the classical and alternative complement pathways when expressed on the surface of Chinese hamster cells but not when expressed as a soluble, truncated protein. (PMID:23482636)
• SUSD4 expression in both breast cancer cells and T cells infiltrating the tumor-associated stroma is useful to predict better prognosis of breast cancer patients. (PMID:26480818)
• Sushi domain-containing protein 4 binds to epithelial growth factor receptor and initiates autophagy in an EGFR phosphorylation independent manner. (PMID:36578014)
• Pan-cancer analysis of Sushi domain-containing protein 4 (SUSD4) and validated in colorectal cancer. (PMID:38579174)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	susd4	ENSDARG00000026335
mus_musculus	Susd4	ENSMUSG00000038576
rattus_norvegicus	Susd4	ENSRNOG00000003562

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), 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

Sushi domain-containing protein 4 — Q5VX71 (reviewed: Q5VX71)

All UniProt accessions (9): Q5VX71, A0A140VK55, A0A7P0T864, A0A7P0T8V7, A0A7P0Z409, A0A7P0Z457, B7Z369, V9GYN8, V9GZ49

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.

Subcellular location. Membrane Secreted.

Tissue specificity. Isoform 3 is the predominant isoform in all tissues except cortex, cerebellum, kidney, and breast. Isoform 1 is found primarily in the esophagus and the brain.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5VX71-1	1, SUSD4a	yes
Q5VX71-2	2
Q5VX71-3	3, SUSD4b
Q5VX71-4	4

RefSeq proteins (3): NP_001032252, NP_001397858, NP_060452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR042985	SUSD4	Family

Pfam: PF00084

UniProt features (30 total): disulfide bond 8, splice variant 6, domain 4, glycosylation site 3, region of interest 2, compositionally biased region 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VX71-F1	71.72	0.38

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 (8): 57–99, 85–117, 122–165, 147–177, 180–224, 210–237, 243–289, 274–302

Glycosylation sites (3): 104, 134, 192

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION

GO Biological Process (7): complement activation, classical pathway (GO:0006958), regulation of complement activation (GO:0030449), innate immune response (GO:0045087), negative regulation of complement activation, alternative pathway (GO:0045957), negative regulation of complement activation, classical pathway (GO:0045959), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), immune system process (GO:0002376)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), postsynaptic membrane (GO:0045211), parallel fiber to Purkinje cell synapse (GO:0098688), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	2
negative regulation of complement activation	2
cellular anatomical structure	2
humoral immune response mediated by circulating immunoglobulin	1
regulation of immune effector process	1
regulation of humoral immune response	1
immune response	1
defense response to symbiont	1
complement activation, alternative pathway	1
regulation of complement activation, alternative pathway	1
negative regulation of innate immune response	1
negative regulation of humoral immune response mediated by circulating immunoglobulin	1
complement activation, classical pathway	1
regulation of complement activation, classical pathway	1
regulation of receptor internalization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1
biological_process	1
binding	1
synaptic membrane	1
postsynapse	1
excitatory synapse	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUSD4	ZNF407	Q9C0G0	551
SUSD4	FHAD1	B1AJZ9	495
SUSD4	SEL1L3	Q68CR1	457
SUSD4	KLHL30	Q0D2K2	444
SUSD4	CDK17	Q00537	429
SUSD4	PGLYRP2	Q96PD5	422
SUSD4	GCSAM	Q8N6F7	421
SUSD4	MGAT4C	Q9UBM8	421
SUSD4	BCAS3	Q9H6U6	419
SUSD4	CAPN8	A6NHC0	413
SUSD4	MS4A15	Q8N5U1	400
SUSD4	DRC8	Q5VUJ9	399
SUSD4	RIBC1	Q8N443	389
SUSD4	TYR	P14679	387
SUSD4	CCDC185	Q8N715	370

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MAPK6	SUSD4	psi-mi:“MI:0915”(physical association)	0.370
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SUSD4	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): CNTNAP3 (Affinity Capture-MS), NNT (Affinity Capture-MS), ATP12A (Affinity Capture-MS), FAT1 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), ITGAV (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), NID2 (Affinity Capture-MS), ENTPD6 (Affinity Capture-MS), ARSK (Affinity Capture-MS), LAMA5 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), KDELC2 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW64, A2AFR3, A4IFL2, A6QLZ5, A8MVS5, A8MWV9, E1BBQ2, E9Q2Z6, O54693, O73612, P01134, P0C8R9, P18519, P48030, P52795, P52796, P98172, Q0VAQ4, Q0VBP7, Q14CM0, Q15223, Q3MHZ5, Q4FZH1, Q4R566, Q5JRV8, Q5R8M2, Q5RB29, Q5T1S8, Q5T292, Q5VX71, Q6AYP5, Q7TPF1, Q8BHW5, Q8BR63, Q8CA71, Q8IVY1, Q8R5M8, Q91WM6, Q91XV6, Q96DD7

Diamond homologs: A0A182C2Z2, A0JNA2, B3EX01, E7FEC4, O08569, O19124, O57254, O62685, O62837, O88174, P08174, P0DTN2, P15529, P21115, P24083, P24084, P36980, P49457, P79138, P81475, Q01227, Q07968, Q28085, Q29RN8, Q4V9Z5, Q53EL9, Q5R4D0, Q5R8M2, Q5VX71, Q60736, Q63515, Q6AX42, Q6P1D5, Q6UXD5, Q7TSK2, Q7Z408, Q8BH32, Q9BYH1, Q9JF44, Q9W332

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2058 predictions. Top by Δscore:

Variant	Effect	Δscore
1:223222216:AATCT:A	acceptor_gain	1.0000
1:223222217:ATCT:A	acceptor_gain	1.0000
1:223222219:CT:C	acceptor_gain	1.0000
1:223222220:TCTG:T	acceptor_loss	1.0000
1:223222221:C:CC	acceptor_gain	1.0000
1:223222221:CT:C	acceptor_loss	1.0000
1:223223243:ACTT:A	donor_loss	1.0000
1:223223244:CTTA:C	donor_loss	1.0000
1:223223245:TTA:T	donor_loss	1.0000
1:223223246:TA:T	donor_loss	1.0000
1:223223247:A:AC	donor_gain	1.0000
1:223223247:AC:A	donor_gain	1.0000
1:223223248:C:CC	donor_gain	1.0000
1:223223248:CC:C	donor_gain	1.0000
1:223223248:CCA:C	donor_gain	1.0000
1:223223248:CCAT:C	donor_gain	1.0000
1:223223546:CAG:C	donor_gain	1.0000
1:223223627:GCCCC:G	acceptor_gain	1.0000
1:223223628:CCCC:C	acceptor_gain	1.0000
1:223223628:CCCCC:C	acceptor_gain	1.0000
1:223223629:CCC:C	acceptor_gain	1.0000
1:223223629:CCCC:C	acceptor_gain	1.0000
1:223223630:CC:C	acceptor_gain	1.0000
1:223223630:CCC:C	acceptor_gain	1.0000
1:223223631:CC:C	acceptor_gain	1.0000
1:223223634:G:C	acceptor_gain	1.0000
1:223227590:TGA:T	donor_loss	1.0000
1:223227591:GAC:G	donor_loss	1.0000
1:223227593:C:CT	donor_loss	1.0000
1:223227631:T:TA	donor_gain	1.0000

AlphaMissense

3212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:223229231:C:A	W294C	1.000
1:223229231:C:G	W294C	1.000
1:223268524:C:A	W171C	1.000
1:223268524:C:G	W171C	1.000
1:223227668:A:C	S329R	0.999
1:223227668:A:T	S329R	0.999
1:223227670:T:G	S329R	0.999
1:223229207:G:C	C302W	0.999
1:223229233:A:G	W294R	0.999
1:223229233:A:T	W294R	0.999
1:223229246:G:C	C289W	0.999
1:223229247:C:G	C289S	0.999
1:223229248:A:G	C289R	0.999
1:223229248:A:T	C289S	0.999
1:223229292:C:T	C274Y	0.999
1:223264664:C:A	W230C	0.999
1:223264664:C:G	W230C	0.999
1:223229208:C:G	C302S	0.998
1:223229208:C:T	C302Y	0.998
1:223229209:A:G	C302R	0.998
1:223229209:A:T	C302S	0.998
1:223229247:C:A	C289F	0.998
1:223229247:C:T	C289Y	0.998
1:223229291:G:C	C274W	0.998
1:223229292:C:A	C274F	0.998
1:223229292:C:G	C274S	0.998
1:223229293:A:G	C274R	0.998
1:223229293:A:T	C274S	0.998
1:223229386:A:G	C243R	0.998
1:223264666:A:G	W230R	0.998

dbSNP variants (sampled 300 via entrez): RS1000028553 (1:223307365 G>A), RS1000046659 (1:223220767 G>C), RS1000049163 (1:223354353 AAG>A), RS1000078720 (1:223358349 A>T), RS1000086316 (1:223353109 C>A), RS1000106631 (1:223347970 C>T), RS1000127692 (1:223358078 C>A,T), RS1000149781 (1:223304100 G>A,C,T), RS1000205371 (1:223255378 G>A,C), RS1000207188 (1:223226442 C>T), RS1000227130 (1:223302640 C>T), RS1000248445 (1:223250126 A>C,G), RS1000316089 (1:223231880 C>G,T), RS1000316755 (1:223275630 G>A,T), RS1000322842 (1:223320968 C>T)

Disease associations

OMIM: gene MIM:615827 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	5
sodium arsenite	affects splicing, decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Estradiol	affects cotreatment, decreases expression, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Tetrachlorodibenzodioxin	decreases expression, increases expression, affects cotreatment	1
Aflatoxin M1	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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