BICRA

Summary

BICRA (BRD4 interacting chromatin remodeling complex associated protein, HGNC:4332) is a protein-coding gene on chromosome 19q13.33, encoding BRD4-interacting chromatin-remodeling complex-associated protein (Q9NZM4). Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.

Enables transcription regulator activator activity. Involved in positive regulation of DNA-templated transcription. Located in nucleus. Part of SWI/SNF complex. Implicated in Coffin-Siris syndrome 12.

Source: NCBI Gene 29998 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Coffin-Siris syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 631 total — 26 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 88
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001394372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4332
Approved symbol	BICRA
Name	BRD4 interacting chromatin remodeling complex associated protein
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SMARCK1
Ensembl gene	ENSG00000063169
Ensembl biotype	protein_coding
OMIM	605690
Entrez	29998

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000396720, ENST00000594866, ENST00000602258, ENST00000614245, ENST00000919879, ENST00000919880

RefSeq mRNA: 2 — MANE Select: NM_001394372 NM_001394372, NM_015711

CCDS: CCDS46134

Canonical transcript exons

ENST00000594866 — 15 exons

Exon	Start	End
ENSE00000363632	47698634	47698782
ENSE00000715251	47681976	47682152
ENSE00000715265	47694115	47694726
ENSE00000715309	47694900	47695080
ENSE00000715337	47695365	47695474
ENSE00000715344	47696451	47696512
ENSE00000864630	47699303	47699405
ENSE00000864631	47698965	47699059
ENSE00000864632	47679321	47681276
ENSE00001642972	47673570	47673615
ENSE00001703284	47673720	47673762
ENSE00001757160	47670443	47670544
ENSE00001771975	47675851	47675916
ENSE00003056972	47609134	47609168
ENSE00003714022	47701328	47703277

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 89.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9694 / max 330.1331, expressed in 1773 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176696	9.2297	1749
176697	1.9211	829
176695	0.8187	424

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	89.81	gold quality
secondary oocyte	CL:0000655	89.67	gold quality
diaphragm	UBERON:0001103	87.25	silver quality
tongue squamous epithelium	UBERON:0006919	85.83	gold quality
germinal epithelium of ovary	UBERON:0001304	85.62	silver quality
vena cava	UBERON:0004087	85.19	silver quality
tibia	UBERON:0000979	84.83	gold quality
gingival epithelium	UBERON:0001949	84.37	silver quality
granulocyte	CL:0000094	84.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.10	silver quality
lower esophagus mucosa	UBERON:0035834	83.89	gold quality
squamous epithelium	UBERON:0006914	83.76	silver quality
pericardium	UBERON:0002407	83.58	gold quality
esophagus squamous epithelium	UBERON:0006920	83.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.03	gold quality
cortical plate	UBERON:0005343	82.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.57	gold quality
visceral pleura	UBERON:0002401	82.52	gold quality
superficial temporal artery	UBERON:0001614	82.50	silver quality
epithelium of esophagus	UBERON:0001976	82.50	silver quality
cardia of stomach	UBERON:0001162	82.42	gold quality
gastrocnemius	UBERON:0001388	82.39	gold quality
medial globus pallidus	UBERON:0002477	82.37	gold quality
jejunal mucosa	UBERON:0000399	82.23	gold quality
cervix squamous epithelium	UBERON:0006922	82.19	silver quality
globus pallidus	UBERON:0001875	81.98	gold quality
body of tongue	UBERON:0011876	81.90	gold quality
hair follicle	UBERON:0002073	81.89	silver quality
ventral tegmental area	UBERON:0002691	81.84	gold quality
thymus	UBERON:0002370	81.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting BICRA, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-9500	98.62	66.54	1845

Literature-anchored findings (GeneRIF, showing 6)

• Polymorphisms in GLTSCR1 are associated with the development of oligodendrogliomas. (PMID:15834925)
• No significant association of GLTSCR1 rs1035938 and lung cancer was found in five genetic models in Chinese population. Haplotypes consisting of PPP1R13L, CD3EAP and GLTSCR1 SNPs on Chr19q13.3 may associate with lung cancer risk in the Chinese population. (PMID:30128886)
• Identifies an acute myeloid leukemia susceptibility locus near BICRA. (PMID:30291333)
• BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. (PMID:33232675)
• GLTSCR1 coordinates alternative splicing and transcription elongation of ZO1 to regulate colorectal cancer progression. (PMID:35218185)
• Identification of a novel BICRA variant leading to the newly described Coffin-Siris syndrome 12. (PMID:36437209)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bicra	ENSDARG00000061159
mus_musculus	Bicra	ENSMUSG00000070808
rattus_norvegicus	Bicra	ENSRNOG00000011262

Paralogs (1): BICRAL (ENSG00000112624)

Protein

Protein identifiers

BRD4-interacting chromatin-remodeling complex-associated protein — Q9NZM4 (reviewed: Q9NZM4)

Alternative names: Glioma tumor suppressor candidate region gene 1 protein

All UniProt accessions (3): Q9NZM4, A0A087WWH3, M0QYC3

UniProt curated annotations — full annotation on UniProt →

Function. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. May play a role in BRD4-mediated gene transcription.

Subunit / interactions. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A. Interacts with BRD4; the interaction bridges BRD4 to the GBAF complex.

Subcellular location. Nucleus.

Tissue specificity. Expressed at moderate levels in heart, brain, placenta, skeletal muscle, and pancreas, and at lower levels in lung, liver and kidney.

Disease relevance. Coffin-Siris syndrome 12 (CSS12) [MIM:619325] A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. CSS12 is an autosomal dominant form characterized by global developmental delay with variably impaired intellectual development, speech and language delay, and behavioral abnormalities, such as autism or hyperactivity. Most CSS12 patients do not have the classic hypoplastic fifth digit/nail abnormalities that are often observed in other forms the disease. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZM4-1	1	yes
Q9NZM4-2	2

RefSeq proteins (2): NP_001381301, NP_056526 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015671	GSCR1_dom	Domain
IPR052438	Chromatin_remod/trans_coact	Family

Pfam: PF15249

UniProt features (36 total): compositionally biased region 15, region of interest 8, sequence variant 6, modified residue 4, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZM4-F1	42.79	0.04

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 (5): 919, 921, 1057, 1413, 1313

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex

MSigDB gene sets: 291 (showing top): AP4_Q6, CAGCTG_AP4_Q5, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_CHROMATIN_REMODELING, AP4_01, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOCC_ATPASE_COMPLEX, GOCC_SWI_SNF_COMPLEX, HSF2_01, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE

GO Biological Process (6): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell differentiation (GO:0045596), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of stem cell population maintenance (GO:1902459)

GO Molecular Function (2): transcription regulator activator activity (GO:0140537), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), SWI/SNF complex (GO:0016514), GBAF complex (GO:0140288)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
cellular anatomical structure	2
SWI/SNF superfamily-type complex	2
chromatin organization	1
transcription by RNA polymerase II	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
stem cell population maintenance	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
regulation of gene expression	1
transcription regulator activity	1
molecular function activator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BICRA	BRD9	Q9H8M2	994
BICRA	BRD4	O60885	788
BICRA	NOP53	Q9NZM5	778
BICRA	ARID2	Q68CP9	772
BICRA	SMARCA4	P51532	757
BICRA	BICRAL	Q6AI39	754
BICRA	SMARCD1	Q96GM5	749
BICRA	SMARCE1	Q969G3	745
BICRA	BRD2	P25440	735
BICRA	DPF1	Q92782	729
BICRA	DPF2	Q92785	720
BICRA	SMARCB1	Q12824	718
BICRA	ARID1B	Q8NFD5	703
BICRA	ARID1A	O14497	701
BICRA	SMARCA2	P51531	691

IntAct

56 interactions, top by confidence:

A	B	Type	Score
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
BICRA	CRK	psi-mi:“MI:0915”(physical association)	0.610
CRK	BICRA	psi-mi:“MI:0407”(direct interaction)	0.610
SS18L2	ARID1A	psi-mi:“MI:2364”(proximity)	0.480
SS18L2	ARID1A	psi-mi:“MI:0914”(association)	0.480
SRC	BICRA	psi-mi:“MI:0915”(physical association)	0.400
GRB2	BICRA	psi-mi:“MI:0915”(physical association)	0.400
BICRA	NCK1	psi-mi:“MI:0915”(physical association)	0.400
BICRA	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
BICRA	PLCG1	psi-mi:“MI:0915”(physical association)	0.400
rep	TAF4	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
SMARCA4	KPNA3	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Proximity Label-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-RNA), GLTSCR1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-Western), GLTSCR1 (Affinity Capture-Western), SMARCA4 (Affinity Capture-Western)

ESM2 similar proteins: A0JME2, A5D7F6, F8VPZ9, O88873, O89090, P08047, P31367, P52591, P54253, P58929, P70178, P78364, Q01714, Q02086, Q07916, Q08E26, Q13227, Q14863, Q2VPU4, Q3U182, Q5E9U0, Q64028, Q66JY2, Q6AI39, Q6T264, Q7Z3K3, Q8BLM0, Q8BZH4, Q8CHH5, Q8CHP6, Q8IXK0, Q8IZL2, Q8K3Z9, Q8K4J6, Q8N196, Q8N1G0, Q8NDX5, Q8QHL5, Q8VHG2, Q91VX2

Diamond homologs: F8VPZ9, Q6AI39, Q8CHH5, Q9NZM4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BICRA	“form complex”	GBAF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
Formation of the canonical BAF (cBAF) complex	6	95.2×	7e-09
Formation of the embryonic stem cell BAF (esBAF) complex	6	90.2×	7e-09
Formation of the non-canonical BAF (ncBAF) complex	5	84.0×	2e-07
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	6	68.5×	3e-08
Downstream signal transduction	6	57.1×	7e-08
Regulation of endogenous retroelements	6	55.3×	7e-08
Regulation of MITF-M-dependent genes involved in pigmentation	6	39.8×	4e-07
MITF-M-dependent gene expression	6	27.2×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	5	67.4×	2e-06
regulation of nucleotide-excision repair	5	60.2×	2e-06
regulation of mitotic metaphase/anaphase transition	5	49.6×	5e-06
positive regulation of stem cell population maintenance	6	41.3×	2e-06
positive regulation of double-strand break repair	5	34.4×	3e-05
regulation of G1/S transition of mitotic cell cycle	5	30.6×	4e-05
negative regulation of cell differentiation	5	28.6×	5e-05
chromatin remodeling	9	13.1×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	24
Uncertain significance	419
Likely benign	108
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1106676	NM_001394372.1(BICRA):c.1993C>T (p.Gln665Ter)	Pathogenic
1106678	NM_001394372.1(BICRA):c.2479_2480delinsA (p.Ala827fs)	Pathogenic
1106681	NM_001394372.1(BICRA):c.192G>C (p.Glu64Asp)	Pathogenic
1218902	NM_001394372.1(BICRA):c.535C>T (p.Gln179Ter)	Pathogenic
1318637	NM_001394372.1(BICRA):c.2075_2078del (p.Thr692fs)	Pathogenic
1685570	NM_001394372.1(BICRA):c.3248+1G>A	Pathogenic
1703502	NM_001394372.1(BICRA):c.3679_3680del (p.Leu1227fs)	Pathogenic
1706314	NM_001394372.1(BICRA):c.1999_2003dup (p.Gly669fs)	Pathogenic
1708048	NM_001394372.1(BICRA):c.974_987dup (p.Gly330fs)	Pathogenic
1801348	NM_001394372.1(BICRA):c.1921C>T (p.Gln641Ter)	Pathogenic
2504582	NM_001394372.1(BICRA):c.639_669del (p.Leu214fs)	Pathogenic
2691554	NM_001394372.1(BICRA):c.3300C>A (p.Tyr1100Ter)	Pathogenic
2692500	NM_001394372.1(BICRA):c.1214_1215insT (p.Gln407fs)	Pathogenic
3376134	NM_001394372.1(BICRA):c.1163del (p.Pro388fs)	Pathogenic
3480632	NM_001394372.1(BICRA):c.1522C>T (p.Gln508Ter)	Pathogenic
3651342	NM_001394372.1(BICRA):c.1846_1852del (p.Ala616fs)	Pathogenic
3775980	NM_001394372.1(BICRA):c.1767_1770del (p.Pro590fs)	Pathogenic
3900398	NM_001394372.1(BICRA):c.3222dup (p.Thr1075fs)	Pathogenic
4279289	GRCh37/hg19 19q13.32-13.33(chr19:47765967-48477463)x1	Pathogenic
4279316	GRCh37/hg19 19q13.32-13.33(chr19:47980688-48251545)x1	Pathogenic
4531728	NM_001394372.1(BICRA):c.706del (p.Gln236fs)	Pathogenic
4531729	NM_001394372.1(BICRA):c.848_849del (p.Gln283fs)	Pathogenic
4536614	NM_001394372.1(BICRA):c.229del (p.Leu77fs)	Pathogenic
4688214	NM_001394372.1(BICRA):c.1074del (p.Leu359fs)	Pathogenic
4839437	NM_001394372.1(BICRA):c.1810C>T (p.Gln604Ter)	Pathogenic
996135	NM_001394372.1(BICRA):c.3247dup (p.Cys1083fs)	Pathogenic
1308646	NM_001394372.1(BICRA):c.386_401del (p.Phe129fs)	Likely pathogenic
1700051	NM_001394372.1(BICRA):c.3529C>T (p.Arg1177Ter)	Likely pathogenic
1700052	NM_001394372.1(BICRA):c.4343dup (p.Pro1449fs)	Likely pathogenic
1801369	NM_001394372.1(BICRA):c.1509_1510insA (p.His504fs)	Likely pathogenic

SpliceAI

3040 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47673541:C:A	acceptor_gain	1.0000
19:47673552:T:TA	acceptor_gain	1.0000
19:47673560:C:G	acceptor_gain	1.0000
19:47673716:CCA:C	acceptor_loss	1.0000
19:47673718:A:AG	acceptor_gain	1.0000
19:47673718:A:AT	acceptor_loss	1.0000
19:47673718:AGT:A	acceptor_gain	1.0000
19:47673719:G:GA	acceptor_gain	1.0000
19:47673719:GT:G	acceptor_gain	1.0000
19:47673719:GTG:G	acceptor_gain	1.0000
19:47673759:GAAG:G	donor_gain	1.0000
19:47673763:G:GG	donor_gain	1.0000
19:47679303:A:AG	acceptor_gain	1.0000
19:47679304:C:G	acceptor_gain	1.0000
19:47679311:C:CA	acceptor_gain	1.0000
19:47679312:G:A	acceptor_gain	1.0000
19:47679319:A:AG	acceptor_gain	1.0000
19:47679320:G:GA	acceptor_gain	1.0000
19:47679320:G:GT	acceptor_loss	1.0000
19:47679320:GCT:G	acceptor_gain	1.0000
19:47679320:GCTC:G	acceptor_gain	1.0000
19:47679320:GCTCC:G	acceptor_gain	1.0000
19:47681278:T:G	donor_loss	1.0000
19:47695456:G:T	donor_gain	1.0000
19:47695470:TGCAG:T	donor_loss	1.0000
19:47695471:GCAGG:G	donor_loss	1.0000
19:47695474:GGTA:G	donor_loss	1.0000
19:47695475:G:GC	donor_loss	1.0000
19:47695476:T:G	donor_loss	1.0000
19:47696448:CAGT:C	acceptor_loss	1.0000

AlphaMissense

831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47673596:T:C	C8R	1.000
19:47673600:T:C	L9S	1.000
19:47673603:T:A	L10Q	1.000
19:47673603:T:C	L10P	1.000
19:47673605:G:C	D11H	1.000
19:47673606:A:C	D11A	1.000
19:47673606:A:G	D11G	1.000
19:47673606:A:T	D11V	1.000
19:47673612:T:A	I13N	1.000
19:47673612:T:C	I13T	1.000
19:47673612:T:G	I13S	1.000
19:47673722:A:G	D15G	1.000
19:47673722:A:T	D15V	1.000
19:47673734:T:A	L19H	1.000
19:47673734:T:C	L19P	1.000
19:47673742:T:C	F22L	1.000
19:47673743:T:C	F22S	1.000
19:47673743:T:G	F22C	1.000
19:47673744:C:A	F22L	1.000
19:47673744:C:G	F22L	1.000
19:47673746:T:C	L23S	1.000
19:47679481:T:A	L104H	1.000
19:47679481:T:C	L104P	1.000
19:47679489:A:C	S107R	1.000
19:47679491:C:A	S107R	1.000
19:47679491:C:G	S107R	1.000
19:47679493:T:A	L108H	1.000
19:47679493:T:C	L108P	1.000
19:47679501:G:C	A111P	1.000
19:47679508:T:A	I113N	1.000

dbSNP variants (sampled 300 via entrez): RS1000016718 (19:47628619 T>A), RS1000028890 (19:47637272 A>C), RS1000034120 (19:47665887 C>A), RS1000052849 (19:47669817 C>G,T), RS1000063398 (19:47663879 A>T), RS1000063876 (19:47637499 C>T), RS1000085034 (19:47669562 A>G), RS1000117232 (19:47633786 T>G), RS1000134353 (19:47701121 C>T), RS1000164005 (19:47632381 G>C), RS1000221564 (19:47627049 C>T), RS1000243112 (19:47666746 A>T), RS1000251473 (19:47623431 A>C,G), RS1000261970 (19:47638816 G>A), RS1000282164 (19:47675973 G>A,C)

Disease associations

OMIM: gene MIM:605690 | disease phenotypes: MIM:619325, MIM:135900, MIM:609943, MIM:614562

GenCC curated gene-disease

Disease	Classification	Inheritance
Coffin-Siris syndrome 12	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Coffin-Siris syndrome	Definitive	AD

Mondo (5): Coffin-Siris syndrome 12 (MONDO:0025699), neurodevelopmental disorder (MONDO:0700092), primary ovarian failure (MONDO:0005387), Coffin-Siris syndrome 1 (MONDO:0007617), intellectual disability (MONDO:0001071)

Orphanet (3): Coffin-Siris syndrome (Orphanet:1465), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000176	Submucous cleft hard palate
HP:0000218	High palate
HP:0000220	Velopharyngeal insufficiency
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000395	Prominent antihelix
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001353_5	HIV-1 susceptibility	8.000000e-07
GCST003801_4	Response to selective serotonin reuptake inhibitors in depression	1.000000e-06
GCST003815_92	Late-onset Alzheimer’s disease	5.000000e-06
GCST008103_65	Bipolar disorder	7.000000e-07
GCST010002_57	Refractive error	1.000000e-27
GCST90013407_48	Liver enzyme levels (gamma-glutamyl transferase)	8.000000e-12
GCST90013423_8	Age-related nuclear cataracts	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:1001870	late-onset Alzheimers disease
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724771 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	Kd	33	nM	MOLIBRESIB
7.16	IC50	70	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179181: Binding affinity against GLTSCR1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0330	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
tebuconazole	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Carcinogens	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects expression	1
Mutagens	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	increases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697336	Binding	Inhibition of GLTSCR1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3K8	N/Tert-1 GLTSCR1	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

300 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,
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities