SPOCD1

Summary

SPOCD1 (SPOC domain containing 1, HGNC:26338) is a protein-coding gene on chromosome 1p35.2, encoding SPOC domain-containing protein 1 (Q6ZMY3). Protein adapter that acts as an essential executor of PIWIL4-piRNA pathway directed transposon DNA methylation and silencing in the male embryonic germ cells.

This gene encodes a protein that belongs to the TFIIS family of transcription factors. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 90853 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 192 total — 3 likely-pathogenic
• MANE Select transcript: NM_144569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26338
Approved symbol	SPOCD1
Name	SPOC domain containing 1
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25348, PPP1R146
Ensembl gene	ENSG00000134668
Ensembl biotype	protein_coding
OMIM	619038
Entrez	90853

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 retained_intron

ENST00000257100, ENST00000360482, ENST00000452755, ENST00000460061, ENST00000468720, ENST00000473361, ENST00000485944, ENST00000525930, ENST00000528579, ENST00000528791, ENST00000529396, ENST00000531039, ENST00000532604, ENST00000533231, ENST00000917879, ENST00000917880

RefSeq mRNA: 6 — MANE Select: NM_144569 NM_001281987, NM_001281988, NM_001394397, NM_001394398, NM_001394399, NM_144569

CCDS: CCDS347, CCDS60066, CCDS72748

Canonical transcript exons

ENST00000360482 — 16 exons

Exon	Start	End
ENSE00001279751	31815961	31816022
ENSE00002699137	31813951	31815372
ENSE00003478516	31796590	31796715
ENSE00003487399	31801664	31801705
ENSE00003550312	31792215	31792401
ENSE00003553210	31799401	31799485
ENSE00003558758	31800441	31800617
ENSE00003560766	31794124	31794235
ENSE00003590664	31798442	31798601
ENSE00003614948	31793278	31793428
ENSE00003626391	31800016	31800141
ENSE00003626433	31790422	31791291
ENSE00003649590	31798207	31798323
ENSE00003669184	31792678	31792767
ENSE00003693302	31793747	31793897
ENSE00003785755	31799809	31799863

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 93.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3583 / max 195.0093, expressed in 1076 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11498	9.6525	977
11497	6.8555	935
11499	0.7512	440
11496	0.0991	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	93.05	gold quality
stromal cell of endometrium	CL:0002255	93.02	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.54	gold quality
left ventricle myocardium	UBERON:0006566	87.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.57	gold quality
monocyte	CL:0000576	80.27	gold quality
right testis	UBERON:0004534	79.96	gold quality
upper lobe of left lung	UBERON:0008952	79.58	gold quality
leukocyte	CL:0000738	79.38	gold quality
left testis	UBERON:0004533	79.37	gold quality
upper arm skin	UBERON:0004263	78.76	gold quality
upper lobe of lung	UBERON:0008948	78.62	gold quality
testis	UBERON:0000473	78.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.18	gold quality
tibia	UBERON:0000979	77.24	gold quality
urinary bladder	UBERON:0001255	77.04	gold quality
epithelial cell of pancreas	CL:0000083	77.03	gold quality
right lung	UBERON:0002167	74.57	gold quality
nasal cavity epithelium	UBERON:0005384	74.23	gold quality
oocyte	CL:0000023	74.18	gold quality
myocardium	UBERON:0002349	74.03	gold quality
cerebellar vermis	UBERON:0004720	73.82	gold quality
myometrium	UBERON:0001296	73.64	gold quality
amniotic fluid	UBERON:0000173	72.95	silver quality
vermiform appendix	UBERON:0001154	72.58	gold quality
right coronary artery	UBERON:0001625	72.14	gold quality
lung	UBERON:0002048	72.06	gold quality
epithelium of nasopharynx	UBERON:0001951	71.75	gold quality
blood	UBERON:0000178	71.65	gold quality
caecum	UBERON:0001153	71.41	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	417.25
E-HCAD-13	yes	25.43
E-ANND-3	yes	14.22
E-MTAB-7249	no	45.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting SPOCD1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978

Literature-anchored findings (GeneRIF, showing 5)

• SPOCD1 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• SPOCD1 genetic variants have role in gastric carcinogenesis. (PMID:28246015)
• SPOCD1 promoted cell proliferation and inhibited cell apoptosis through regulation of VEGFA in osteosarcoma. (PMID:29257309)
• LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1. (PMID:33726799)
• Haplotype phasing of a bipolar disorder pedigree revealed rare multiple mutations of SPOCD1 gene in the 1p36-35 susceptibility locus. (PMID:35504398)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spocd1	ENSMUSG00000028784
rattus_norvegicus		ENSRNOG00000064683
drosophila_melanogaster	pps	FBGN0082831

Paralogs (2): DIDO1 (ENSG00000101191), PHF3 (ENSG00000118482)

Protein

Protein identifiers

SPOC domain-containing protein 1 — Q6ZMY3 (reviewed: Q6ZMY3)

All UniProt accessions (6): Q6ZMY3, E9PKC3, E9PMX0, E9PPM7, E9PQH7, H0YF46

UniProt curated annotations — full annotation on UniProt →

Function. Protein adapter that acts as an essential executor of PIWIL4-piRNA pathway directed transposon DNA methylation and silencing in the male embryonic germ cells. Recruited to young transposons, which are specifically marked with histone H3 trimethylated at both ‘Lys-4’ and ‘Lys-9’ (H3K4me3K9me3), via its association with SPIN1 chromatin reader, and associates with the de novo DNA methylation machinery and repressive chromatin remodeling complexes. Following this, PIWIL4 engages with nascent transposable element transcript to direct piRNA-directed DNA methylation. Not required for piRNA biosynthesis.

Subunit / interactions. Interacts with DNMT3A, DNMT3C and DNMT3L. Interacts with C19orf84. Interacts with SPIN1; promoting recruitment to transposons marked with histone H3 trimethylated at both ‘Lys-4’ and ‘Lys-9’ (H3K4me3K9me3).

Subcellular location. Nucleus. Chromosome.

Disease relevance. Spermatogenic failure. A male infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6ZMY3-1	1	yes
Q6ZMY3-2	2
Q6ZMY3-3	3
Q6ZMY3-4	4
Q6ZMY3-5	5

RefSeq proteins (6): NP_001268916, NP_001268917, NP_001381326, NP_001381327, NP_001381328, NP_653170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003618	TFIIS_cen_dom	Domain
IPR012921	SPOC_C	Domain
IPR036575	TFIIS_cen_dom_sf	Homologous_superfamily

Pfam: PF07500, PF07744

UniProt features (34 total): compositionally biased region 9, splice variant 9, region of interest 8, sequence variant 4, domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMY3-F1	47.76	0.05

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
R-HSA-9842860	Regulation of endogenous retroelements

MSigDB gene sets: 88 (showing top): GOBP_MALE_GAMETE_GENERATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, HENDRICKS_SMARCA4_TARGETS_UP, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, chr1p35, WANG_SMARCE1_TARGETS_UP, CHICAS_RB1_TARGETS_CONFLUENT, MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_DN, GOBP_TRANSPOSITION, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7

GO Biological Process (7): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), transposable element silencing by piRNA-mediated heterochromatin formation (GO:0141006), transposable element silencing by piRNA-mediated DNA methylation (GO:0141196), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of endogenous retroelements	1
Gene expression (Transcription)	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transposable element silencing by heterochromatin formation	2
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
piRNA-mediated heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
negative regulation of gene expression	1
protein binding	1
molecular adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPOCD1	DNMT3L	Q9UJW3	739
SPOCD1	BANF1	O75531	627
SPOCD1	TEX15	Q9BXT5	545
SPOCD1	ZKSCAN2	Q63HK3	543
SPOCD1	SPEN	Q96T58	528
SPOCD1	DNMT3A	Q9Y6K1	506
SPOCD1	TDRD9	Q8NDG6	487
SPOCD1	G3BP1	Q13283	485
SPOCD1	TCEA3	O75764	462
SPOCD1	DNAJC9	Q8WXX5	458
SPOCD1	SH2D5	Q6ZV89	456
SPOCD1	TCEA1	P23193	445
SPOCD1	TSPYL5	Q86VY4	432
SPOCD1	TASOR	Q9UK61	400
SPOCD1	PIWIL4	Q7Z3Z4	392

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PPP1CA	SPOCD1	psi-mi:“MI:0407”(direct interaction)	0.440
SPOCD1	PPP1CC	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): SPOCD1 (Affinity Capture-RNA), SPOCD1 (Negative Genetic), SPOCD1 (Cross-Linking-MS (XL-MS)), SPOCD1 (Two-hybrid), SPOCD1 (Affinity Capture-Western)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A2VE02, A5D7I0, A6NDY2, A6NGG8, A6NIJ5, A6NNJ1, A8MXJ8, A8MYA2, B1ASB6, B2RW88, D6RGX4, O60269, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV75, P0DV76, Q2KIS6, Q2NL68, Q3SY00, Q4R736, Q4V8B5, Q5RCQ2, Q5SZB4, Q5VZ46, Q5XIK6, Q658T7, Q66JV7, Q6NS69, Q6PAC4, Q6ZMY3, Q76N32, Q7TSA6, Q7Z591, Q80VW7, Q80X53

Diamond homologs: A6ZZW1, O44498, O75764, P10711, P20232, P23193, P36106, P52652, Q29RL9, Q2KI09, Q4KLL0, Q6FJ00, Q6ZMY3, Q9U263, B1ASB6, Q148K0, Q15560, Q92576, P23881, Q08923, Q1MTR4, Q63799, Q6C0K9, Q99MY8, Q9NR48, Q9QVN7, Q9ZVH8, B8AMA8, O74508, Q12830, Q5EA28, Q5EAW9, Q5F489, Q5HZG4, Q5VWG9, Q6BER5, Q84TV4, Q8C9B9, Q9BTC0, Q9CWW7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	150
Likely benign	27
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2626778	NM_144569.7(SPOCD1):c.2912T>G (p.Leu971Arg)	Likely pathogenic
2626779	NM_144569.7(SPOCD1):c.3354_3355insA (p.Gln1119fs)	Likely pathogenic
2626780	NM_144569.7(SPOCD1):c.1991_1992del (p.Arg664fs)	Likely pathogenic

SpliceAI

2640 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31792398:CGTC:C	acceptor_gain	1.0000
1:31792673:GGTAC:G	donor_loss	1.0000
1:31792674:GTACC:G	donor_loss	1.0000
1:31792675:TA:T	donor_loss	1.0000
1:31792676:A:AG	donor_loss	1.0000
1:31792677:C:CT	donor_loss	1.0000
1:31792767:CCT:C	acceptor_loss	1.0000
1:31792769:T:G	acceptor_loss	1.0000
1:31793750:T:TA	donor_gain	1.0000
1:31793775:C:A	donor_gain	1.0000
1:31793776:C:A	donor_gain	1.0000
1:31796587:A:AC	donor_gain	1.0000
1:31796587:AAC:A	donor_gain	1.0000
1:31796588:A:C	donor_gain	1.0000
1:31798202:CTCA:C	donor_loss	1.0000
1:31798203:TCA:T	donor_loss	1.0000
1:31798204:CA:C	donor_loss	1.0000
1:31798205:A:AC	donor_gain	1.0000
1:31798205:AC:A	donor_gain	1.0000
1:31798205:ACC:A	donor_gain	1.0000
1:31798206:C:CC	donor_gain	1.0000
1:31798206:CC:C	donor_gain	1.0000
1:31798206:CCC:C	donor_gain	1.0000
1:31792400:TC:T	acceptor_gain	0.9900
1:31792401:CC:C	acceptor_gain	0.9900
1:31792402:C:CC	acceptor_gain	0.9900
1:31792402:CT:C	acceptor_loss	0.9900
1:31792406:G:T	acceptor_gain	0.9900
1:31792407:G:C	acceptor_gain	0.9900
1:31792407:G:GC	acceptor_gain	0.9900

AlphaMissense

7839 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31793326:G:C	F879L	0.990
1:31793326:G:T	F879L	0.990
1:31793327:A:G	F879S	0.990
1:31793328:A:G	F879L	0.990
1:31798466:G:C	F668L	0.989
1:31798466:G:T	F668L	0.989
1:31798468:A:G	F668L	0.989
1:31798461:A:G	L670P	0.986
1:31798277:A:G	L692P	0.985
1:31793341:G:C	F874L	0.983
1:31793341:G:T	F874L	0.983
1:31793343:A:G	F874L	0.983
1:31793362:C:A	W867C	0.981
1:31793362:C:G	W867C	0.981
1:31798473:A:G	L666P	0.981
1:31798483:A:C	Y663D	0.981
1:31798479:C:G	R664P	0.979
1:31798475:G:C	S665R	0.978
1:31798475:G:T	S665R	0.978
1:31798477:T:G	S665R	0.978
1:31793364:A:G	W867R	0.976
1:31793364:A:T	W867R	0.976
1:31798226:C:G	R709P	0.975
1:31798253:A:G	L700P	0.974
1:31798463:G:C	N669K	0.973
1:31798463:G:T	N669K	0.973
1:31798535:C:A	E645D	0.973
1:31798535:C:G	E645D	0.973
1:31792255:G:C	F974L	0.972
1:31792255:G:T	F974L	0.972

dbSNP variants (sampled 300 via entrez): RS1000002055 (1:31803340 A>G,T), RS1000021286 (1:31799323 A>T), RS1000021424 (1:31796838 A>C,G), RS1000081534 (1:31798001 C>T), RS1000404494 (1:31816011 G>A), RS1000435551 (1:31815740 T>C), RS1000560817 (1:31799603 C>G), RS1000839941 (1:31790262 AC>A), RS1001141687 (1:31790549 A>G), RS1001197165 (1:31806965 T>C), RS1001302878 (1:31799647 GCCCCCACCCCTT>G), RS1001463743 (1:31813505 C>T), RS1001472182 (1:31817107 T>TATATATATAC), RS1001493654 (1:31794427 C>A), RS1001526042 (1:31793195 C>T)

Disease associations

OMIM: gene MIM:619038 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_36	Body mass index	9.000000e-10
GCST009798_61	Asthma	3.000000e-08
GCST012227_1393	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
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

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, increases reaction	4
bisphenol A	decreases expression, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
lead acetate	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	increases expression	1
ormosil	increases expression, affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression, increases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8W5	Ubigene HCT 116 SPOCD1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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