SIN3B

Summary

SIN3B (SIN3 transcription regulator family member B, HGNC:19354) is a protein-coding gene on chromosome 19p13.11, encoding Paired amphipathic helix protein Sin3b (O75182). Acts as a transcriptional repressor.

Predicted to enable transcription corepressor activity. Predicted to be involved in cardiac muscle tissue development; negative regulation of transcription by RNA polymerase II; and skeletal muscle tissue development. Predicted to be located in nucleus. Predicted to be part of Sin3-type complex. Predicted to be active in chromatin.

Source: NCBI Gene 23309 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 288 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_001297595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19354
Approved symbol	SIN3B
Name	SIN3 transcription regulator family member B
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0700
Ensembl gene	ENSG00000127511
Ensembl biotype	protein_coding
OMIM	607777
Entrez	23309

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000248054, ENST00000379803, ENST00000594235, ENST00000594372, ENST00000595049, ENST00000595541, ENST00000595900, ENST00000596638, ENST00000596802, ENST00000599880, ENST00000601141, ENST00000602204, ENST00000880627, ENST00000880628, ENST00000880629, ENST00000880630, ENST00000880631, ENST00000924994

RefSeq mRNA: 3 — MANE Select: NM_001297595 NM_001297595, NM_001297597, NM_015260

CCDS: CCDS32946, CCDS74308, CCDS77254

Canonical transcript exons

ENST00000248054 — 19 exons

Exon	Start	End
ENSE00000494565	16846970	16847113
ENSE00000689611	16865410	16865648
ENSE00000689615	16862352	16862559
ENSE00000689616	16854143	16854261
ENSE00000689623	16841768	16841968
ENSE00000689627	16829791	16829897
ENSE00000873487	16851412	16851534
ENSE00000873488	16853069	16853158
ENSE00000873492	16876055	16876228
ENSE00000951802	16831494	16831647
ENSE00000951804	16869460	16870075
ENSE00003032596	16878497	16880349
ENSE00003175050	16829398	16829540
ENSE00003467439	16876486	16876578
ENSE00003498330	16866373	16866556
ENSE00003515624	16878183	16878390
ENSE00003579213	16871229	16871398
ENSE00003588282	16863680	16863796
ENSE00003661724	16877545	16877639

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.7486 / max 434.1932, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174443	41.7486	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	97.38	gold quality
right uterine tube	UBERON:0001302	97.11	gold quality
right ovary	UBERON:0002118	97.05	gold quality
left ovary	UBERON:0002119	96.91	gold quality
endocervix	UBERON:0000458	96.84	gold quality
right lung	UBERON:0002167	96.82	gold quality
mucosa of stomach	UBERON:0001199	96.66	gold quality
left uterine tube	UBERON:0001303	96.45	gold quality
left testis	UBERON:0004533	96.31	gold quality
sural nerve	UBERON:0015488	96.29	gold quality
right testis	UBERON:0004534	96.14	gold quality
metanephros cortex	UBERON:0010533	95.99	gold quality
nerve	UBERON:0001021	95.92	gold quality
tibial nerve	UBERON:0001323	95.92	gold quality
ectocervix	UBERON:0012249	95.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.78	gold quality
left lobe of thyroid gland	UBERON:0001120	95.67	gold quality
right frontal lobe	UBERON:0002810	95.31	gold quality
right lobe of thyroid gland	UBERON:0001119	95.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.19	gold quality
cerebellar hemisphere	UBERON:0002245	95.06	gold quality
granulocyte	CL:0000094	95.01	gold quality
upper lobe of left lung	UBERON:0008952	94.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.88	gold quality
lower esophagus	UBERON:0013473	94.87	gold quality
cerebellar cortex	UBERON:0002129	94.81	gold quality
adenohypophysis	UBERON:0002196	94.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.35	gold quality
minor salivary gland	UBERON:0001830	94.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDK4
NCL
SRD5A1

Upstream regulators (CollecTRI, top): MXD1, RFX5, TP53

miRNA regulators (miRDB)

46 targeting SIN3B, 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-4283	100.00	66.42	2097
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914

Literature-anchored findings (GeneRIF, showing 18)

• SMAR1 regulates cyclin D1 by modification of chromatin through the SIN3/histone deacetylase 1 complex (PMID:16166625)
• The interaction between SIN3B and ETO required an intact amino-terminus of ETO and the NHR2 domain. (PMID:18205948)
• ETO family member-mediated oligomerization and repression can be distinct events and that interaction between ETO family members and hSIN3B or N-CoR may not necessarily strengthen transcriptional repression. (PMID:18586123)
• Modulation of Sin3B-associated activities may represent new therapeutic opportunities for treatment of cancers. (PMID:19654306)
• disruption of the function of a specific Sin3A/B domain leads to epigenetic reprogramming and derepression of specific subsets of genes in breast cancer cells (PMID:20547842)
• identification of a mammalian complex containing the corepressor Sin3B, the histone deacetylase HDAC1, Mrg15, and the PHD finger-containing Pf1 (PMID:21041482)
• the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes (PMID:22028823)
• Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression (PMID:24691445)
• this study highlights an essential role for Sin3B in IFN-c induced COL1A2 repression in smooth muscle cells. (PMID:24709079)
• A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. (PMID:24951594)
• The study suggests that the difference in the conformation of native state structure or structural flexibility of the paired amphi pathic helices (PAH) domains of Sin3B might be responsible for interacting with specific binding partners. (PMID:25869359)
• High mRNA expression of SIN3A/low mRNA expression of SIN3B correlates with longer relapse free survival specifically in patients with triple negative breast cancer. (PMID:27780928)
• Low SIN3B expression is associated with Prostate Cancer Progression. (PMID:28807943)
• These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence. (PMID:30517867)
• Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network. (PMID:32467258)
• Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer. (PMID:33652591)
• Haploinsufficiency of the Sin3/HDAC corepressor complex member SIN3B causes a syndromic intellectual disability/autism spectrum disorder. (PMID:33811806)
• Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex. (PMID:37137925)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sin3b	ENSDARG00000062472
mus_musculus	Sin3b	ENSMUSG00000031622
drosophila_melanogaster	Sin3A	FBGN0022764
caenorhabditis_elegans	sin-3	WBGENE00004117

Paralogs (1): SIN3A (ENSG00000169375)

Protein

Protein identifiers

Paired amphipathic helix protein Sin3b — O75182 (reviewed: O75182)

Alternative names: Histone deacetylase complex subunit Sin3b, Transcriptional corepressor Sin3b

All UniProt accessions (3): O75182, M0QYC5, M0R271

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression. As part of the SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2. SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription.

Subunit / interactions. Component of the SIN3B complex, which includes SIN3B, HDAC2 or HDAC1, PHF12 and MORF4L1. Interacts with FOXK1/MNF, MXI, MAD, NCOR1 and SAP30. Interaction with SUDS3 enhances the interaction with HDAC1 to form a complex. Interacts with CRY1, HCFC1, MAD3, MAD4, MAEL, REST, RNF220 and SETDB1. Interacts with C6orf89. Interacts with MYT1L.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated by RNF220 that leads to proteasomal degradation.

Isoforms (3)

UniProt ID	Names	Canonical?
O75182-1	1, Long	yes
O75182-2	2
O75182-3	3

RefSeq proteins (3): NP_001284524, NP_001284526, NP_056075 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003822	PAH	Repeat
IPR013194	HDAC_interact_dom	Domain
IPR031693	Sin3_C	Domain
IPR036600	PAH_sf	Homologous_superfamily
IPR039774	Sin3-like	Family

Pfam: PF02671, PF08295, PF16879

UniProt features (61 total): helix 25, region of interest 10, strand 9, turn 6, domain 3, compositionally biased region 3, modified residue 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8BPB	ELECTRON MICROSCOPY	2.8
8BPC	ELECTRON MICROSCOPY	2.8
8C60	ELECTRON MICROSCOPY	3.4
8BPA	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75182-F1	69.07	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.

Post-translational modifications (2): 709, 712

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1

MSigDB gene sets: 183 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, PID_HDAC_CLASSI_PATHWAY, PID_TELOMERASE_PATHWAY, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, BILD_E2F3_ONCOGENIC_SIGNATURE, WONG_ENDMETRIUM_CANCER_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX1_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_UP, BIOCARTA_ETS_PATHWAY, RODRIGUES_DCC_TARGETS_DN, GOMF_CHROMATIN_BINDING, GOCC_SEX_CHROMOSOME, LIU_SOX4_TARGETS_DN, GOCC_SIN3_TYPE_COMPLEX

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cell migration (GO:0030336), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), X chromosome (GO:0000805), Y chromosome (GO:0000806), XY body (GO:0001741), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), autosome (GO:0030849), Sin3-type complex (GO:0070822)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Gene expression (Transcription)	2
Negative epigenetic regulation of rRNA expression	1
Transcriptional regulation by RUNX1	1
Metabolism of lipids	1
Cellular response to chemical stress	1
RNA Polymerase II Transcription	1
Epigenetic regulation of gene expression	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sex chromosome	3
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
binding	2
chromosome	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
condensed chromatin of inactivated sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
histone deacetylase complex	1
nuclear chromosome	1
chromatin	1

Protein interactions and networks

STRING

2348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIN3B	SAP30	O75446	996
SIN3B	HDAC1	Q13547	996
SIN3B	HDAC2	Q92769	992
SIN3B	RBBP4	P31149	984
SIN3B	SUDS3	Q9H7L9	982
SIN3B	SAP18	O00422	971
SIN3B	RBBP7	Q16576	971
SIN3B	SIN3A	Q96ST3	927
SIN3B	ARID4B	Q4LE39	866
SIN3B	NCOR1	O75376	819
SIN3B	MECP2	P51608	808
SIN3B	FOXK1	P85037	791
SIN3B	IKZF1	Q13422	780
SIN3B	ARID4A	P29374	776
SIN3B	RCOR1	Q9UKL0	775

IntAct

92 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
KDM5A	SIN3B	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
HDAC2	SIN3B	psi-mi:“MI:0914”(association)	0.640
MYC	SIN3B	psi-mi:“MI:0915”(physical association)	0.610
SIN3B	MYC	psi-mi:“MI:0403”(colocalization)	0.610
MYC	SIN3B	psi-mi:“MI:2364”(proximity)	0.610
MYC	SIN3B	psi-mi:“MI:0914”(association)	0.610
SIN3B	MYC	psi-mi:“MI:0914”(association)	0.610
SIN3B	TNRC18	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530

BioGRID (231): SIN3B (Affinity Capture-Western), BRMS1 (Affinity Capture-Western), SIN3B (Protein-peptide), SIN3B (Affinity Capture-MS), SIN3B (Affinity Capture-MS), SIN3B (Affinity Capture-MS), SIN3B (Affinity Capture-MS), SIN3B (Co-fractionation), ACTN4 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), KDM5A (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), STX3 (Affinity Capture-MS), SAP30 (Affinity Capture-MS), AKAP12 (Affinity Capture-MS)

ESM2 similar proteins: A0A7P0TBJ1, A0A804C8T0, A2BE76, A2RRV3, A4IG66, A4IIE8, D4A4K3, O75182, P57095, P97578, Q02225, Q08AY9, Q09YG9, Q09YK4, Q1JPG0, Q28C41, Q2IBF8, Q2QL82, Q2QLF8, Q2QLG9, Q4QQM5, Q503U3, Q5BLE2, Q5M836, Q5XJS0, Q62141, Q62671, Q68EF0, Q6DFB7, Q6GR21, Q6NRB7, Q6P7D5, Q6PCG6, Q7L4E1, Q86YS3, Q8BG30, Q8BHS8, Q8BK03, Q8BQP8, Q8NAN2

Diamond homologs: O04539, O13919, O48686, O75182, Q60520, Q62141, Q96ST3, Q9LFQ3, Q9SRH9, Q9SZ67, Q9XIE1, Q9XIK6, O74755, Q09750, A5JYW9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SIN3B	“down-regulates activity”	TP53	binding
SIN3B	“form complex”	Sin3B_complex	binding
RNF220	“down-regulates quantity by destabilization”	SIN3B	polyubiquitination
MYT1L	“up-regulates activity”	SIN3B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	5	45.7×	4e-06
Regulation of PTEN gene transcription	6	21.4×	2e-05
HDACs deacetylate histones	8	19.2×	6e-07
Potential therapeutics for SARS	8	18.3×	7e-07
Chromatin organization	11	17.9×	5e-09
Chromatin modifying enzymes	11	15.9×	1e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	14.6×	6e-04
NuRD complex assembly	5	14.1×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	10	109.4×	3e-16
positive regulation of stem cell population maintenance	11	54.0×	2e-14
negative regulation of transforming growth factor beta receptor signaling pathway	10	24.8×	8e-10
negative regulation of cell migration	10	15.9×	5e-08
chromatin remodeling	15	15.6×	5e-12
chromatin organization	7	9.9×	3e-04
regulation of gene expression	6	7.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	231
Likely benign	35
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4056086	NM_001297595.2(SIN3B):c.382-2A>G	Pathogenic
4813565	NM_001297595.2(SIN3B):c.625_656dup (p.Phe221fs)	Pathogenic
3776074	NM_001297595.2(SIN3B):c.2950C>T (p.Gln984Ter)	Likely pathogenic

SpliceAI

3360 predictions. Top by Δscore:

Variant	Effect	Δscore
19:16829541:G:GG	donor_gain	1.0000
19:16829787:GCAG:G	acceptor_loss	1.0000
19:16829790:G:T	acceptor_loss	1.0000
19:16829893:CAGAG:C	donor_loss	1.0000
19:16829894:AGAGG:A	donor_loss	1.0000
19:16829895:GAG:G	donor_gain	1.0000
19:16829895:GAGG:G	donor_loss	1.0000
19:16829896:AG:A	donor_loss	1.0000
19:16829897:GGTA:G	donor_loss	1.0000
19:16829898:G:C	donor_loss	1.0000
19:16829899:T:A	donor_loss	1.0000
19:16831492:A:AG	acceptor_gain	1.0000
19:16831493:G:GG	acceptor_gain	1.0000
19:16831493:GCATC:G	acceptor_gain	1.0000
19:16841767:GGAGA:G	acceptor_gain	1.0000
19:16841967:AGGTA:A	donor_loss	1.0000
19:16841969:G:GG	donor_gain	1.0000
19:16841969:GTA:G	donor_loss	1.0000
19:16841970:T:A	donor_loss	1.0000
19:16846957:T:A	acceptor_gain	1.0000
19:16846960:A:AG	acceptor_gain	1.0000
19:16846961:A:AG	acceptor_gain	1.0000
19:16846962:A:AG	acceptor_gain	1.0000
19:16846963:C:G	acceptor_gain	1.0000
19:16846964:T:TA	acceptor_gain	1.0000
19:16846965:GGCA:G	acceptor_loss	1.0000
19:16846966:GCA:G	acceptor_loss	1.0000
19:16846968:A:AG	acceptor_gain	1.0000
19:16846969:G:GG	acceptor_gain	1.0000
19:16847114:G:GG	donor_gain	1.0000

AlphaMissense

7458 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:16829804:T:A	L45H	1.000
19:16829804:T:C	L45P	1.000
19:16829809:T:C	Y47H	1.000
19:16829809:T:G	Y47D	1.000
19:16829813:T:A	L48Q	1.000
19:16829813:T:C	L48P	1.000
19:16829854:T:G	Y62D	1.000
19:16829863:T:C	F65L	1.000
19:16829864:T:C	F65S	1.000
19:16829864:T:G	F65C	1.000
19:16829865:C:A	F65L	1.000
19:16829865:C:G	F65L	1.000
19:16829867:T:C	L66P	1.000
19:16829876:T:A	M69K	1.000
19:16829876:T:C	M69T	1.000
19:16829876:T:G	M69R	1.000
19:16829884:T:C	F72L	1.000
19:16829885:T:C	F72S	1.000
19:16829885:T:G	F72C	1.000
19:16829886:C:A	F72L	1.000
19:16829886:C:G	F72L	1.000
19:16831511:T:A	V82D	1.000
19:16831520:G:C	R85P	1.000
19:16831523:T:A	V86D	1.000
19:16831532:T:C	L89P	1.000
19:16831534:T:C	F90L	1.000
19:16831535:T:C	F90S	1.000
19:16831536:C:A	F90L	1.000
19:16831536:C:G	F90L	1.000
19:16831553:T:C	L96P	1.000

dbSNP variants (sampled 300 via entrez): RS1000321579 (19:16851667 G>A,T), RS1000346585 (19:16871489 A>C,G,T), RS1000486336 (19:16845547 A>G), RS1000713068 (19:16850437 T>C), RS1000764998 (19:16855570 A>T), RS1000821843 (19:16846690 C>T), RS1000932450 (19:16840907 A>G), RS1000943732 (19:16858107 C>A), RS1000973281 (19:16860821 C>T), RS1000986944 (19:16835109 A>G), RS1001040991 (19:16835614 G>A), RS1001061017 (19:16850664 C>T), RS1001125248 (19:16866648 G>A,T), RS1001186439 (19:16852290 T>TG), RS1001191868 (19:16869252 G>A,T)

Disease associations

OMIM: gene MIM:607777 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
SIN3A-related intellectual disability syndrome due to a point mutation	Supportive	Autosomal dominant
syndromic intellectual disability	Limited	Autosomal dominant

Mondo (4): neurodevelopmental disorder (MONDO:0700092), coloboma (MONDO:0001476), SIN3A-related intellectual disability syndrome due to a point mutation (MONDO:0044700), syndromic intellectual disability (MONDO:0000508)

Orphanet (1): OBSOLETE: Ocular coloboma (Orphanet:194)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000164	Abnormality of the dentition
HP:0000365	Hearing impairment
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000924	Abnormality of the skeletal system
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001382	Joint hypermobility
HP:0001808	Fragile nails
HP:0001999	Abnormal facial shape
HP:0002119	Ventriculomegaly
HP:0002213	Fine hair
HP:0002500	Abnormal cerebral white matter morphology
HP:0002750	Delayed skeletal maturation
HP:0006989	Dysplastic corpus callosum
HP:0030084	Clinodactyly
HP:0032059	Mild malformation of cortical development
HP:0040195	Decreased head circumference
HP:0410263	Brain imaging abnormality

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
hexamethylene bisacetamide	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases reaction, affects binding, increases reaction	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	decreases expression	1
Benzo(a)pyrene	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice