SUSD3

Summary

SUSD3 (sushi domain containing 3, HGNC:28391) is a protein-coding gene on chromosome 9q22.31, encoding Sushi domain-containing protein 3 (Q96L08). May play a role in breast tumorigenesis by promoting estrogen-dependent cell proliferation, cell-cell interactions and migration.

Located in plasma membrane.

Source: NCBI Gene 203328 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_145006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28391
Approved symbol	SUSD3
Name	sushi domain containing 3
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC26847
Ensembl gene	ENSG00000157303
Ensembl biotype	protein_coding
OMIM	616429
Entrez	203328

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000375469, ENST00000375472, ENST00000465709, ENST00000471462, ENST00000617293, ENST00000913799

RefSeq mRNA: 5 — MANE Select: NM_145006 NM_001287005, NM_001287006, NM_001287007, NM_001287008, NM_145006

CCDS: CCDS6701, CCDS69620, CCDS75857

Canonical transcript exons

ENST00000375472 — 5 exons

Exon	Start	End
ENSE00001031728	93075784	93075972
ENSE00001467195	93058701	93058830
ENSE00001877753	93084537	93085133
ENSE00003559918	93077846	93077993
ENSE00003575002	93079471	93079602

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5885 / max 492.4731, expressed in 1008 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97381	9.4307	997
97384	0.1578	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.35	gold quality
left testis	UBERON:0004533	95.98	gold quality
testis	UBERON:0000473	94.42	gold quality
oocyte	CL:0000023	93.56	gold quality
bone marrow cell	CL:0002092	92.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.69	gold quality
granulocyte	CL:0000094	91.62	gold quality
right uterine tube	UBERON:0001302	91.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.01	gold quality
right ovary	UBERON:0002118	90.27	gold quality
spleen	UBERON:0002106	89.89	gold quality
lymph node	UBERON:0000029	89.87	gold quality
left uterine tube	UBERON:0001303	89.75	gold quality
secondary oocyte	CL:0000655	89.58	gold quality
left ovary	UBERON:0002119	89.36	gold quality
body of uterus	UBERON:0009853	87.05	gold quality
blood	UBERON:0000178	86.34	gold quality
bone marrow	UBERON:0002371	86.26	gold quality
ovary	UBERON:0000992	86.16	gold quality
vermiform appendix	UBERON:0001154	85.34	gold quality
right lobe of liver	UBERON:0001114	84.88	gold quality
leukocyte	CL:0000738	83.94	gold quality
monocyte	CL:0000576	83.22	gold quality
endocervix	UBERON:0000458	82.37	gold quality
adult mammalian kidney	UBERON:0000082	82.04	gold quality
fallopian tube	UBERON:0003889	80.94	gold quality
stromal cell of endometrium	CL:0002255	80.30	gold quality
ectocervix	UBERON:0012249	79.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.74	gold quality
adult organism	UBERON:0007023	79.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	34.97
E-ANND-3	yes	7.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting SUSD3, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895
HSA-MIR-28-3P	96.42	67.18	579
HSA-MIR-7848-3P	95.69	65.00	363

Literature-anchored findings (GeneRIF, showing 2)

• Data indicate that sushi domain containing 3 (SUSD3) is a promoter of estrogen-dependent cell proliferation and regulator of cell-cell and cell-substrate interactions and migration in breast cancer. (PMID:24413080)
• High expression of SUSD3 is associated with breast cancer. (PMID:26745129)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Susd3	ENSMUSG00000021384
rattus_norvegicus	Susd3	ENSRNOG00000016525

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), C8A (ENSG00000157131), 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 3 — Q96L08 (reviewed: Q96L08)

All UniProt accessions (4): Q96L08, A0A087WVN2, S4R3T3, S4R444

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in breast tumorigenesis by promoting estrogen-dependent cell proliferation, cell-cell interactions and migration.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in estrogen receptor-positive breast tumors.

Induction. Up-regulated upon treatment with estradiol in MCF-7 cells.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96L08-1	1	yes
Q96L08-2	2
Q96L08-3	3

RefSeq proteins (5): NP_001273934, NP_001273935, NP_001273936, NP_001273937, NP_659443* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR053067	SUSD3	Family

Pfam: PF00084

UniProt features (15 total): topological domain 2, disulfide bond 2, splice variant 2, sequence variant 2, region of interest 2, chain 1, transmembrane region 1, domain 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96L08-F1	69.45	0.25

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 (2): 61–91, 32–75

Glycosylation sites (1): 27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, chr9q22, GARY_CD5_TARGETS_UP, PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_DN, NUYTTEN_NIPP1_TARGETS_DN, CHEN_METABOLIC_SYNDROM_NETWORK, LI_INDUCED_T_TO_NATURAL_KILLER_UP, MARTENS_BOUND_BY_PML_RARA_FUSION, WIERENGA_STAT5A_TARGETS_DN, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP, BHAT_ESR1_TARGETS_VIA_AKT1_UP, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, GSE13522_WT_VS_IFNAR_KO_SKIN_DN, ZFP3_TARGET_GENES, ZNF184_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUSD3	FGD3	Q5JSP0	540
SUSD3	LRRC66	Q68CR7	526
SUSD3	NAGLU	P54802	422
SUSD3	KRTCAP3	Q53RY4	422
SUSD3	ESYT3	A0FGR9	402
SUSD3	GLYATL2	Q8WU03	398
SUSD3	ACY3	Q96HD9	376
SUSD3	CLSTN1	O94985	369
SUSD3	RASAL3	Q86YV0	355
SUSD3	MOSPD1	Q9UJG1	350
SUSD3	SASH3	O75995	342
SUSD3	ACBD7	Q8N6N7	340
SUSD3	TMEM126B	Q8IUX1	328
SUSD3	PRRT3	Q5FWE3	324
SUSD3	LARGE2	Q8N3Y3	324

IntAct

80 interactions, top by confidence:

A	B	Type	Score
SMAGP	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
RPRM	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	TMEM98	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	TMEM47	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
TMEM182	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
CLDN23	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
PLP1	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
TMED8	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	HHATL	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	TMEM147	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
KTN1	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	TMPRSS4	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	RPRM	psi-mi:“MI:0915”(physical association)	0.560
CNIH3	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SEC22A	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	SUSD3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (86): TRIM29 (Affinity Capture-MS), SBSN (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGHG1 (Affinity Capture-MS), SCGB1D1 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), TYMP (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), S100A7A (Affinity Capture-MS), S100A7 (Affinity Capture-MS), PPL (Affinity Capture-MS), IVL (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), TMEM51 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GSZ0, A0A1B0GUA5, A0A1B0GVQ0, A0A1B0GVT2, A0JNM1, A2A9G7, A2APA5, A2VE22, A6NLX4, A7E1Z1, A7MB05, A9CBA0, D3ZR35, E9Q942, F5HI25, O39519, P06480, P09517, P0DJ93, P18345, Q0II74, Q0VFL4, Q1RMT9, Q2T9Z2, Q498C7, Q56A20, Q5BIR3, Q5RCS3, Q5XIF1, Q67593, Q6UWT2, Q6UWV7, Q7TMJ8, Q80WB0, Q80WK2, Q86UW2, Q8K1D8, Q8N5W8, Q8TEF2, Q8VEA7

Diamond homologs: Q96L08, Q9D176, Q29RN8, Q4V9Z5, Q6UXD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1213 predictions. Top by Δscore:

Variant	Effect	Δscore
9:93075973:G:GG	donor_gain	1.0000
9:93077991:CAGG:C	donor_loss	1.0000
9:93079470:GGTCA:G	acceptor_gain	1.0000
9:93079603:G:GG	donor_gain	1.0000
9:93082197:GGCA:G	donor_gain	1.0000
9:93082200:A:G	donor_gain	1.0000
9:93084535:A:AG	acceptor_gain	1.0000
9:93084536:G:GG	acceptor_gain	1.0000
9:93084536:GA:G	acceptor_gain	1.0000
9:93059171:G:GT	donor_gain	0.9900
9:93059171:G:T	donor_gain	0.9900
9:93059410:G:GT	donor_gain	0.9900
9:93075931:G:T	donor_gain	0.9900
9:93075969:AAACG:A	donor_loss	0.9900
9:93075970:AAC:A	donor_gain	0.9900
9:93075970:AACG:A	donor_loss	0.9900
9:93075971:AC:A	donor_gain	0.9900
9:93075972:CG:C	donor_loss	0.9900
9:93075973:G:GA	donor_loss	0.9900
9:93075974:T:G	donor_loss	0.9900
9:93077842:ACAGT:A	acceptor_gain	0.9900
9:93077844:A:AG	acceptor_gain	0.9900
9:93077844:AGT:A	acceptor_gain	0.9900
9:93077845:G:GG	acceptor_gain	0.9900
9:93077845:GTG:G	acceptor_gain	0.9900
9:93077995:T:G	donor_loss	0.9900
9:93079466:TCCA:T	acceptor_loss	0.9900
9:93079467:CCA:C	acceptor_loss	0.9900
9:93079468:CAG:C	acceptor_loss	0.9900
9:93079468:CAGGT:C	acceptor_gain	0.9900

AlphaMissense

1653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:93077902:A:C	S112R	0.998
9:93077904:C:A	S112R	0.998
9:93077904:C:G	S112R	0.998
9:93075947:G:C	W84C	0.996
9:93075947:G:T	W84C	0.996
9:93075945:T:A	W84R	0.989
9:93075945:T:C	W84R	0.989
9:93077935:T:C	F123L	0.986
9:93077937:C:A	F123L	0.986
9:93077937:C:G	F123L	0.986
9:93077905:T:C	C113R	0.978
9:93075918:T:A	C75S	0.977
9:93075919:G:C	C75S	0.977
9:93075919:G:A	C75Y	0.976
9:93075920:C:G	C75W	0.975
9:93077903:G:A	S112N	0.972
9:93077882:C:A	A105D	0.971
9:93077891:C:A	A108D	0.969
9:93075918:T:C	C75R	0.968
9:93075966:T:A	C91S	0.963
9:93075967:G:C	C91S	0.963
9:93075876:T:A	C61S	0.962
9:93075876:T:C	C61R	0.962
9:93075877:G:C	C61S	0.962
9:93077924:T:G	M119R	0.961
9:93075926:G:C	W77C	0.958
9:93075926:G:T	W77C	0.958
9:93077924:T:A	M119K	0.958
9:93075919:G:T	C75F	0.957
9:93077915:T:A	I116N	0.955

dbSNP variants (sampled 300 via entrez): RS1000181180 (9:93071302 A>G), RS1000225592 (9:93060860 A>G,T), RS1000241023 (9:93077557 C>A,T), RS1000406804 (9:93083668 G>A), RS1000417047 (9:93082449 C>T), RS1000494933 (9:93061248 T>G), RS1000588173 (9:93078662 A>T), RS1000597844 (9:93066541 C>T), RS1000671391 (9:93066316 C>T), RS1000698906 (9:93084772 G>C,T), RS1000783370 (9:93072539 G>A), RS1000844472 (9:93061536 G>C), RS1000866507 (9:93077981 G>A), RS1000893014 (9:93061668 A>G), RS1000986026 (9:93085030 C>T)

Disease associations

OMIM: gene MIM:616429 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002400_382	Plateletcrit	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs76292544	SUSD3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	9
Benzo(a)pyrene	increases methylation, decreases expression	5
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	decreases expression, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Calcitriol	increases expression	1
Copper	affects binding, decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

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