DCST2

Summary

DCST2 (DC-STAMP domain containing 2, HGNC:26562) is a protein-coding gene on chromosome 1q21.3, encoding DC-STAMP domain-containing protein 2 (Q5T1A1). Essential sperm cell-surface protein required for sperm-egg fusion and fertilization.

Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and sperm-egg recognition. Predicted to be located in acrosomal membrane.

Source: NCBI Gene 127579 — RefSeq curated summary.

At a glance

• GWAS associations: 47
• Clinical variants (ClinVar): 184 total
• MANE Select transcript: NM_144622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26562
Approved symbol	DCST2
Name	DC-STAMP domain containing 2
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32934
Ensembl gene	ENSG00000163354
Ensembl biotype	protein_coding
OMIM	619861
Entrez	127579

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding

ENST00000368423, ENST00000368424, ENST00000467991, ENST00000485982, ENST00000498036

RefSeq mRNA: 1 — MANE Select: NM_144622 NM_144622

CCDS: CCDS1082

Canonical transcript exons

ENST00000368424 — 15 exons

Exon	Start	End
ENSE00001073688	155031169	155031234
ENSE00001073690	155032667	155032768
ENSE00001073698	155033094	155033264
ENSE00001073701	155030432	155030645
ENSE00001073704	155031574	155031771
ENSE00001852891	155018527	155018760
ENSE00002176765	155033434	155033781
ENSE00003458531	155029233	155029397
ENSE00003476191	155023117	155023257
ENSE00003484939	155026302	155026402
ENSE00003497659	155030084	155030241
ENSE00003500680	155023832	155023959
ENSE00003522499	155026548	155026715
ENSE00003565312	155023364	155023457
ENSE00003606590	155024472	155024602

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 84.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0330 / max 18.6825, expressed in 8 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14891	0.0188	3
14893	0.0075	3
14894	0.0034	2
14892	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	84.80	gold quality
left testis	UBERON:0004533	83.90	gold quality
skin of abdomen	UBERON:0001416	83.04	gold quality
skin of leg	UBERON:0001511	81.41	gold quality
testis	UBERON:0000473	80.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.23	gold quality
lower esophagus mucosa	UBERON:0035834	79.49	gold quality
zone of skin	UBERON:0000014	77.47	gold quality
ectocervix	UBERON:0012249	75.39	gold quality
tibial nerve	UBERON:0001323	75.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.16	gold quality
right lobe of liver	UBERON:0001114	74.11	gold quality
endocervix	UBERON:0000458	73.95	gold quality
minor salivary gland	UBERON:0001830	73.91	gold quality
vagina	UBERON:0000996	73.86	gold quality
mucosa of transverse colon	UBERON:0004991	73.62	gold quality
esophagus mucosa	UBERON:0002469	72.54	gold quality
granulocyte	CL:0000094	71.47	gold quality
transverse colon	UBERON:0001157	71.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.53	gold quality
mouth mucosa	UBERON:0003729	70.38	gold quality
saliva-secreting gland	UBERON:0001044	69.28	gold quality
right uterine tube	UBERON:0001302	69.22	gold quality
body of uterus	UBERON:0009853	69.05	gold quality
cerebellar hemisphere	UBERON:0002245	68.99	gold quality
left ovary	UBERON:0002119	68.89	gold quality
cerebellar cortex	UBERON:0002129	68.80	gold quality
body of stomach	UBERON:0001161	68.73	gold quality
uterine cervix	UBERON:0000002	68.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	47.13
E-ANND-3	no	2.20

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• OS9 is critically involved in the modulation of ER-to-Golgi transport of DC-STAMP in response to TLR triggering, suggesting a novel role for OS9 in myeloid differentiation and cell fusion. (PMID:18952287)
• This study highlights that common variation in DCST2 influences variation in early growth and adult height. (PMID:25281659)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcst2	ENSDARG00000088693
mus_musculus	Dcst2	ENSMUSG00000109293
rattus_norvegicus	Dcst2	ENSRNOG00000058618
drosophila_melanogaster	CG6845	FBGN0035099
drosophila_melanogaster	CG32320	FBGN0052320

Paralogs (3): OCSTAMP (ENSG00000149635), DCST1 (ENSG00000163357), DCSTAMP (ENSG00000164935)

Protein

Protein identifiers

DC-STAMP domain-containing protein 2 — Q5T1A1 (reviewed: Q5T1A1)

All UniProt accessions (2): H0YF62, Q5T1A1

UniProt curated annotations — full annotation on UniProt →

Function. Essential sperm cell-surface protein required for sperm-egg fusion and fertilization.

Subunit / interactions. Interacts with DCST1.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T1A1-1	1	yes
Q5T1A1-2	2

RefSeq proteins (1): NP_653223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012858	DC_STAMP-like	Domain
IPR051856	CSR-E3_Ligase_Protein	Family
IPR058842	DCST1_C	Domain

Pfam: PF07782, PF26037, PF26039

UniProt features (22 total): topological domain 7, transmembrane region 6, glycosylation site 3, compositionally biased region 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T1A1-F1	73.49	0.17

Functional residue map

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

Glycosylation sites (3): 284, 296, 480

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_SPERM_EGG_RECOGNITION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOCC_ACROSOMAL_MEMBRANE, GOCC_SECRETORY_VESICLE, chr1q21, GOCC_SECRETORY_GRANULE_MEMBRANE

GO Biological Process (2): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), sperm-egg recognition (GO:0035036)

GO Molecular Function (0):

GO Cellular Component (3): acrosomal membrane (GO:0002080), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	2
cellular process involved in reproduction in multicellular organism	1
cell-cell recognition	1
acrosomal vesicle	1
secretory granule membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCST2	SPACA6	W5XKT8	747
DCST2	TMEM95	Q3KNT9	688
DCST2	IZUMO1	Q8IYV9	613
DCST2	PBXIP1	Q96AQ6	478
DCST2	CLGN	O14967	472
DCST2	SPACA4	Q8TDM5	441
DCST2	LENEP	Q9Y5L5	377
DCST2	ENTREP3	P81408	370
DCST2	IZUMO1R	A6ND01	368
DCST2	LCN12	Q6JVE5	367
DCST2	HAGHL	Q6PII5	355
DCST2	COBLL1	Q53SF7	350
DCST2	SUMF1	Q8NBK3	347
DCST2	FOLR2	P14207	347
DCST2	SNX10	Q9Y5X0	344

IntAct

0 interactions, top by confidence:

BioGRID (2): DCST2 (Affinity Capture-MS), DCST2 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: A0A140LIJ0, Q5T1A1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	159
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2908 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155030430:A:AC	donor_gain	1.0000
1:155030431:C:CC	donor_gain	1.0000
1:155032661:GCTTA:G	donor_loss	1.0000
1:155032662:CTTAC:C	donor_loss	1.0000
1:155032663:TTA:T	donor_loss	1.0000
1:155032664:TAC:T	donor_loss	1.0000
1:155032665:A:AC	donor_gain	1.0000
1:155032666:C:CC	donor_gain	1.0000
1:155032666:C:CT	donor_loss	1.0000
1:155032666:CCTAT:C	donor_gain	1.0000
1:155033087:GACTT:G	donor_loss	1.0000
1:155033088:ACTTA:A	donor_loss	1.0000
1:155033090:TTAC:T	donor_loss	1.0000
1:155033091:TA:T	donor_loss	1.0000
1:155033092:A:AC	donor_gain	1.0000
1:155033092:A:C	donor_loss	1.0000
1:155033093:C:A	donor_loss	1.0000
1:155033093:C:CG	donor_gain	1.0000
1:155033093:CT:C	donor_gain	1.0000
1:155033093:CTG:C	donor_gain	1.0000
1:155033093:CTGA:C	donor_gain	1.0000
1:155033432:A:AC	donor_gain	1.0000
1:155033433:C:CC	donor_gain	1.0000
1:155023107:T:TA	donor_gain	0.9900
1:155023363:CAG:C	donor_gain	0.9900
1:155026296:CCTCA:C	donor_loss	0.9900
1:155026297:CTCA:C	donor_loss	0.9900
1:155026298:TCA:T	donor_loss	0.9900
1:155026299:CA:C	donor_loss	0.9900
1:155026301:C:A	donor_loss	0.9900

AlphaMissense

4979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155031720:C:G	C198S	0.992
1:155031721:A:T	C198S	0.992
1:155033188:G:C	N115K	0.991
1:155033188:G:T	N115K	0.991
1:155030602:G:C	F283L	0.989
1:155030602:G:T	F283L	0.989
1:155030604:A:G	F283L	0.989
1:155031687:C:G	C209S	0.989
1:155031688:A:T	C209S	0.989
1:155031720:C:T	C198Y	0.989
1:155031588:C:G	C242S	0.988
1:155031589:A:T	C242S	0.988
1:155031688:A:G	C209R	0.988
1:155031721:A:G	C198R	0.988
1:155031588:C:T	C242Y	0.987
1:155031589:A:G	C242R	0.986
1:155033501:G:C	S67R	0.983
1:155033501:G:T	S67R	0.983
1:155033503:T:G	S67R	0.983
1:155030603:A:G	F283S	0.982
1:155029285:G:C	F430L	0.981
1:155029285:G:T	F430L	0.981
1:155029287:A:G	F430L	0.981
1:155031219:C:T	C252Y	0.981
1:155031621:C:T	C231Y	0.981
1:155031622:A:G	C231R	0.981
1:155030173:A:G	F363S	0.979
1:155031219:C:G	C252S	0.979
1:155031220:A:T	C252S	0.979
1:155031719:G:C	C198W	0.979

dbSNP variants (sampled 300 via entrez): RS1000459606 (1:155035634 AAG>A), RS1000511302 (1:155035228 TCTCAG>T), RS1000911822 (1:155023330 G>T), RS1000962254 (1:155022745 CAAACAAAACA>C,CAAACA,CAAACAAAACAAAACA), RS1001199649 (1:155029636 T>C), RS1001250372 (1:155029352 T>G), RS1001477850 (1:155029562 A>G), RS1001585934 (1:155022799 G>C), RS1001794559 (1:155035169 T>C), RS1002426642 (1:155028193 T>C), RS1002919916 (1:155019740 C>T), RS1003016361 (1:155019145 G>A), RS1003278663 (1:155020005 G>A,T), RS1003526149 (1:155024265 A>G), RS1003539466 (1:155031019 G>C,T)

Disease associations

OMIM: gene MIM:619861 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST001942_19	Prostate cancer	2.000000e-08
GCST002644_1	Birth length	2.000000e-08
GCST002782_131	Waist-to-hip ratio adjusted for body mass index	5.000000e-10
GCST002782_132	Waist-to-hip ratio adjusted for body mass index	7.000000e-10
GCST002782_133	Waist-to-hip ratio adjusted for body mass index	3.000000e-10
GCST002782_62	Waist-to-hip ratio adjusted for body mass index	3.000000e-10
GCST004505_33	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	6.000000e-07
GCST004505_34	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	2.000000e-06
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST008103_81	Bipolar disorder	1.000000e-06
GCST008362_141	Birth weight	7.000000e-11
GCST008362_91	Birth weight	3.000000e-19
GCST008363_17	Offspring birth weight	3.000000e-08
GCST008363_22	Offspring birth weight	1.000000e-07
GCST010242_258	HDL cholesterol levels	1.000000e-09
GCST010303_17	Nevus count or cutaneous melanoma	2.000000e-18
GCST010304_26	Cutaneous malignant melanoma	4.000000e-15
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0006784	body height at birth
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0004341	body fat distribution
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004632	nevus count
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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