SAP25

Summary

SAP25 (Sin3A associated protein 25, HGNC:41908) is a protein-coding gene on chromosome 7q22.1, encoding Histone deacetylase complex subunit SAP25 (Q8TEE9). Involved in the transcriptional repression mediated by the mSIN3A but not the N-CoR corepressor complex.

Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to be located in cytoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 100316904 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001348680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:41908
Approved symbol	SAP25
Name	Sin3A associated protein 25
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00248
Ensembl gene	ENSG00000205307
Ensembl biotype	protein_coding
OMIM	619230
Entrez	100316904

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000538735, ENST00000611464, ENST00000614631, ENST00000622764

RefSeq mRNA: 3 — MANE Select: NM_001348680 NM_001168682, NM_001348677, NM_001348680

CCDS: CCDS55137, CCDS87529

Canonical transcript exons

ENST00000622764 — 6 exons

Exon	Start	End
ENSE00003466345	100572654	100572751
ENSE00003606400	100572228	100572571
ENSE00003669453	100572860	100573013
ENSE00003717104	100573297	100573400
ENSE00003729553	100573597	100573900
ENSE00003785625	100573106	100573212

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 95.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7106 / max 265.1746, expressed in 36 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85213	0.4746	35
85212	0.2360	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.00	gold quality
spleen	UBERON:0002106	93.32	gold quality
blood	UBERON:0000178	92.79	gold quality
lower esophagus mucosa	UBERON:0035834	90.07	gold quality
right uterine tube	UBERON:0001302	88.99	gold quality
right testis	UBERON:0004534	87.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.24	gold quality
lymph node	UBERON:0000029	87.05	gold quality
pituitary gland	UBERON:0000007	86.70	gold quality
right ovary	UBERON:0002118	86.55	gold quality
left testis	UBERON:0004533	86.50	gold quality
adenohypophysis	UBERON:0002196	86.22	gold quality
left ovary	UBERON:0002119	86.18	gold quality
right lobe of thyroid gland	UBERON:0001119	86.04	gold quality
tibial nerve	UBERON:0001323	85.95	gold quality
testis	UBERON:0000473	85.92	gold quality
left lobe of thyroid gland	UBERON:0001120	85.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.60	gold quality
thyroid gland	UBERON:0002046	85.21	gold quality
cerebellar hemisphere	UBERON:0002245	84.97	gold quality
endocervix	UBERON:0000458	84.82	gold quality
cerebellar cortex	UBERON:0002129	84.78	gold quality
cerebellum	UBERON:0002037	84.70	gold quality
ovary	UBERON:0000992	84.52	gold quality
mucosa of transverse colon	UBERON:0004991	83.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.67	gold quality
vermiform appendix	UBERON:0001154	83.64	gold quality
upper lobe of left lung	UBERON:0008952	83.41	gold quality
bone marrow	UBERON:0002371	83.40	gold quality
small intestine	UBERON:0002108	82.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	78.12
E-ANND-3	no	1.81

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Distinct Regions within SAP25 Recruit O-Linked Glycosylation, DNA Demethylation, and Ubiquitin Ligase and Hydrolase Activities to the Sin3/HDAC Complex. (PMID:39435885)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sap25	ENSMUSG00000079165
rattus_norvegicus		ENSRNOG00000089441

Protein

Protein identifiers

Histone deacetylase complex subunit SAP25 — Q8TEE9 (reviewed: Q8TEE9)

Alternative names: 25 kDa Sin3-associated polypeptide, Sin3 corepressor complex subunit SAP25

All UniProt accessions (2): Q8TEE9, A0A087WYF9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the transcriptional repression mediated by the mSIN3A but not the N-CoR corepressor complex.

Subunit / interactions. May be a component of the mSIN3A corepressor complex. Interacts with SIN3A. Interacts with HDAC2.

Subcellular location. Nucleus. Cytoplasm.

RefSeq proteins (3): NP_001162153, NP_001335606, NP_001335609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029163	SAP25	Family

Pfam: PF15476

UniProt features (4 total): compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEE9-F1	57.58	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 22 (showing top): KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, SENGUPTA_EBNA1_ANTICORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, PBXIP1_TARGET_GENES, SNRNP70_TARGET_GENES, chr7q22, GAO_LARGE_INTESTINE_ADULT_CE_OLFM4HIGH_STEM_CELL, ZNF740_TARGET_GENES, NAKAYA_MYELOID_DENDRITIC_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_UP

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAP25	SAP30	O75446	692
SAP25	SIN3A	Q96ST3	631
SAP25	SAP30L	Q9HAJ7	612
SAP25	ARID4B	Q4LE39	530
SAP25	BRMS1	Q9HCU9	506
SAP25	BRMS1L	Q5PSV4	501
SAP25	HDAC1	Q13547	493
SAP25	RBBP4	P31149	492
SAP25	SUDS3	Q9H7L9	473
SAP25	ING1	Q9UK53	434
SAP25	REST	Q13127	418
SAP25	SAP18	O00422	403
SAP25	CCER2	I3L3R5	397
SAP25	RHBDD3	Q9Y3P4	371
SAP25	MECP2	P51608	362

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SAP25	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
SIN3A	SAP25	psi-mi:“MI:0915”(physical association)	0.400
Sap25	DDX3X	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): SIN3A (Reconstituted Complex), SAP25 (Reconstituted Complex), SIN3A (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), SAP25 (Affinity Capture-Western), GTF2B (Affinity Capture-MS), PML (Affinity Capture-MS), TTLL12 (Affinity Capture-MS), OGT (Affinity Capture-MS), SIN3A (Affinity Capture-MS), CDK4 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), ZC3HAV1 (Affinity Capture-MS), LPCAT1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: Q1EHW4, Q8TEE9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

531 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100572750:CC:C	acceptor_gain	1.0000
7:100572751:CC:C	acceptor_gain	1.0000
7:100572648:TCTCA:T	donor_loss	0.9900
7:100572649:CTCA:C	donor_loss	0.9900
7:100572650:TCA:T	donor_loss	0.9900
7:100572651:CACCT:C	donor_loss	0.9900
7:100572652:A:C	donor_loss	0.9900
7:100572653:C:CA	donor_loss	0.9900
7:100572653:CCTG:C	donor_gain	0.9900
7:100572749:ACC:A	acceptor_gain	0.9900
7:100572749:ACCC:A	acceptor_loss	0.9900
7:100572750:CCC:C	acceptor_gain	0.9900
7:100572752:C:CC	acceptor_gain	0.9900
7:100572753:T:G	acceptor_loss	0.9900
7:100573101:CTCA:C	donor_loss	0.9900
7:100573103:CAC:C	donor_loss	0.9900
7:100573104:A:AC	donor_gain	0.9900
7:100573104:A:T	donor_loss	0.9900
7:100573104:AC:A	donor_gain	0.9900
7:100573105:C:CC	donor_gain	0.9900
7:100573105:C:G	donor_loss	0.9900
7:100573105:CC:C	donor_gain	0.9900
7:100573105:CCCA:C	donor_gain	0.9900
7:100572747:GAACC:G	acceptor_gain	0.9800
7:100572752:C:T	acceptor_gain	0.9800
7:100572855:GGTAC:G	donor_loss	0.9800
7:100572856:GTACC:G	donor_loss	0.9800
7:100572857:TACC:T	donor_loss	0.9800
7:100572858:ACCT:A	donor_loss	0.9800
7:100572859:CCTGC:C	donor_loss	0.9800

AlphaMissense

1878 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100572720:G:C	F83L	0.985
7:100572720:G:T	F83L	0.985
7:100572722:A:G	F83L	0.985
7:100572453:G:T	A145D	0.960
7:100572721:A:G	F83S	0.954
7:100572963:G:C	H38Q	0.947
7:100572963:G:T	H38Q	0.947
7:100572450:A:T	L146H	0.945
7:100572964:T:C	H38R	0.940
7:100572441:A:G	L149P	0.936
7:100572428:G:C	S153R	0.935
7:100572428:G:T	S153R	0.935
7:100572430:T:G	S153R	0.935
7:100572721:A:C	F83C	0.933
7:100572712:T:C	D86G	0.928
7:100572459:A:G	L143P	0.927
7:100572461:C:A	E142D	0.927
7:100572461:C:G	E142D	0.927
7:100572441:A:T	L149Q	0.922
7:100572462:T:A	E142V	0.921
7:100572438:A:G	L150P	0.917
7:100572712:T:A	D86V	0.906
7:100572450:A:G	L146P	0.902
7:100572441:A:C	L149R	0.889
7:100573150:A:G	W7R	0.884
7:100573150:A:T	W7R	0.884
7:100572984:G:C	F31L	0.882
7:100572984:G:T	F31L	0.882
7:100572986:A:G	F31L	0.882
7:100572722:A:T	F83I	0.880

dbSNP variants (sampled 300 via entrez): RS1000014443 (7:100573435 G>A,T), RS1000116950 (7:100574325 T>C), RS1000446188 (7:100574090 T>C), RS1000620119 (7:100572285 G>A,T), RS1001051589 (7:100574981 G>A,T), RS1001627956 (7:100575808 T>C), RS1001743966 (7:100575558 C>T), RS1003640889 (7:100573997 GCT>G), RS1003755634 (7:100573842 C>T), RS1003955442 (7:100572028 C>T), RS1004560364 (7:100574669 T>C), RS1005035934 (7:100574907 G>A), RS1005799532 (7:100574019 G>A,C), RS1006819205 (7:100573284 G>A,C), RS1008736998 (7:100574599 C>A,G)

Disease associations

OMIM: gene MIM:619230 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
abrine	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Estradiol	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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