SRCAP

Summary

SRCAP (Snf2 related CREBBP activator protein, HGNC:16974) is a protein-coding gene on chromosome 16p11.2, encoding Chromatin remodeling protein SRCAP (Q6ZRS2). Acts both as a chromatin remodeler and transcription coregulator. It is a common-essential gene (DepMap: required in 95.7% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features.

Source: NCBI Gene 10847 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Floating-Harbor syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 2,440 total — 42 pathogenic, 60 likely-pathogenic
• Phenotypes (HPO): 129
• Cancer dependency (DepMap): dependent in 95.7% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16974
Approved symbol	SRCAP
Name	Snf2 related CREBBP activator protein
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0309, SWR1, DOMO1
Ensembl gene	ENSG00000080603
Ensembl biotype	protein_coding
OMIM	611421
Entrez	10847

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000262518, ENST00000411466, ENST00000474008, ENST00000483083, ENST00000706321, ENST00000931587, ENST00000931588, ENST00000931589, ENST00000931590, ENST00000931591

RefSeq mRNA: 1 — MANE Select: NM_006662 NM_006662

CCDS: CCDS10689

Canonical transcript exons

ENST00000262518 — 34 exons

Exon	Start	End
ENSE00001484698	30699908	30699981
ENSE00001484700	30699171	30699242
ENSE00001664800	30704064	30704315
ENSE00002301530	30700616	30700878
ENSE00003995536	30713208	30713377
ENSE00003995537	30712679	30712815
ENSE00003995538	30713519	30713711
ENSE00003995539	30722563	30722748
ENSE00003995540	30722963	30723229
ENSE00003995541	30722122	30722286
ENSE00003995542	30737049	30741409
ENSE00003995543	30733280	30733449
ENSE00003995544	30716293	30716479
ENSE00003995545	30728966	30729231
ENSE00003995546	30711571	30711744
ENSE00003995547	30729370	30729572
ENSE00003995548	30709851	30710128
ENSE00003995549	30733602	30733798
ENSE00003995550	30710999	30711088
ENSE00003995551	30716066	30716202
ENSE00003995552	30709513	30709735
ENSE00003995553	30712262	30712439
ENSE00003995554	30720162	30720331
ENSE00003995555	30734496	30734615
ENSE00003995556	30710754	30710847
ENSE00003995557	30720713	30720978
ENSE00003995558	30711835	30712157
ENSE00003995559	30707572	30707712
ENSE00003995561	30721189	30721476
ENSE00003995562	30733894	30734008
ENSE00003995563	30736541	30736624
ENSE00003995564	30723584	30725082
ENSE00003995565	30736200	30736394
ENSE00003995566	30707183	30707368

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 91.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1891 / max 252.8718, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153707	11.5494	1794
153709	6.8967	1696
153708	2.7589	1395
153711	1.6909	883
153710	0.2932	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	91.88	gold quality
stromal cell of endometrium	CL:0002255	89.00	gold quality
granulocyte	CL:0000094	88.34	gold quality
colonic epithelium	UBERON:0000397	88.33	gold quality
vermiform appendix	UBERON:0001154	86.80	gold quality
body of uterus	UBERON:0009853	86.40	gold quality
mucosa of stomach	UBERON:0001199	86.16	gold quality
apex of heart	UBERON:0002098	86.08	gold quality
gastrocnemius	UBERON:0001388	86.06	gold quality
cortical plate	UBERON:0005343	85.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.70	gold quality
muscle of leg	UBERON:0001383	85.65	gold quality
bone marrow cell	CL:0002092	85.54	gold quality
right adrenal gland cortex	UBERON:0035827	85.36	gold quality
diaphragm	UBERON:0001103	85.32	gold quality
right lobe of thyroid gland	UBERON:0001119	85.06	gold quality
right adrenal gland	UBERON:0001233	85.05	gold quality
left adrenal gland	UBERON:0001234	84.84	gold quality
popliteal artery	UBERON:0002250	84.74	gold quality
tibial artery	UBERON:0007610	84.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.60	gold quality
lower esophagus	UBERON:0013473	84.57	gold quality
ventricular zone	UBERON:0003053	84.46	gold quality
left adrenal gland cortex	UBERON:0035825	84.46	gold quality
body of stomach	UBERON:0001161	84.45	gold quality
ganglionic eminence	UBERON:0004023	84.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.42	gold quality
minor salivary gland	UBERON:0001830	84.40	gold quality
left lobe of thyroid gland	UBERON:0001120	84.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.67

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
KLK3	Activation
PCK2	Unknown

Upstream regulators (CollecTRI, top): AR, FOXC1

miRNA regulators (miRDB)

46 targeting SRCAP, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-7113-3P	98.75	65.71	1120

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 95.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 24)

• SRCAP functions as a coactivator to regulate transcription initiated by several signaling pathways. (PMID:14500758)
• Results identify YL1 as a subunit of the TRRAP/TIP60 HAT complex, and also as a component of a novel mammalian multiprotein complex that includes the SNF2-related helicase SRCAP. (PMID:15647280)
• SRCAP is implicated in developmental gene activation (PMID:16024792)
• SRCAP-containing complex supports ATP-dependent exchange of histone dimers containing H2B and H2A.Z into mononucleosomes reconstituted with recombinant H2A, H2B, H3, and H4. (PMID:16634648)
• Methods for purification and assay of the SRCAP chromatin remodeling complexes are described. (PMID:17101442)
• SRCAP is recruited to promoters and is critical for the deposition of H2A.Z. (PMID:17617668)
• These data identify SRCAP as a physiologically relevant mediator of PSA expression, and demonstrate that SRCAP plays a role in prostate cancer cell proliferation. (PMID:20432434)
• HCV NS3 protein is involved in the activation of the Notch-signaling pathway through the targeting to both SRCAP and p400 (PMID:21673954)
• Sanger sequencing identified mutations in SRCAP in eight more affected persons. (PMID:22265015)
• Our genome-wide expression results demonstrate that SRCAP-mediated H2A.Z deposition at promoter regions is necessary for complete gene reactivation induced by DNA demethylation. (PMID:22479200)
• Data indicate that the absence of SRCAP mutations in 3/9 cases suggesting genetic heterogeneity of floating-harbor syndrome (FH syndrome). (PMID:22965468)
• Sequencing of the SRCAP gene demonstrated a de novo mutation matching one of the known FHS-associated mutations. (PMID:23165645)
• Functional studies and reports of patients with additional SRCAP mutations will eventually lead to a better understanding of biological mechanisms underlying this disorder. (PMID:23763483)
• These results indicate that perturbed skeletal maturation from infancy through adolescence is a characteristic feature in patients with SRCAP mutations. (PMID:24375913)
• This study implicates the human SRCAP chromatin remodeling complex as a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs in the context of chromatin. (PMID:25176633)
• Data confirm a mutational hot spot in the final exon of SRCAP in the majority of Floating-Harbor syndrome patients but also show that exon 33 of this gene can be affected. (PMID:25433523)
• Alterative hypotheses to explain how the Srcap truncating mutations lead to the onset of Floating-Harbor syndrome are presented. (PMID:27208210)
• Data show that PCI domain-containing protein 2 (Pcid2) controls lymphoid lineage commitment through the regulation of Snf2-related CREBBP activator protein (SRCAP) remodelling activity. (PMID:29138493)
• cryo-EM structure of human SRCAP complex (PMID:30337683)
• Cancer-related SRCAP and TPR mutations in colon cancers. (PMID:33307343)
• Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature. (PMID:33909990)
• Systematic analysis of exonic germline and postzygotic de novo mutations in bipolar disorder. (PMID:34145229)
• LINC00665 sponges miR-641 to promote the progression of breast cancer by targeting the SNF2-related CREBBP activator protein (SRCAP). (PMID:35152838)
• SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation. (PMID:37863054)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srcap	ENSDARG00000005236
mus_musculus	Srcap	ENSMUSG00000053877
rattus_norvegicus	Srcap	ENSRNOG00000050282

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

Chromatin remodeling protein SRCAP — Q6ZRS2 (reviewed: Q6ZRS2)

Alternative names: Domino homolog 2, Snf2-related CBP activator

All UniProt accessions (3): Q6ZRS2, A0A087X0E3, C9J4U4

UniProt curated annotations — full annotation on UniProt →

Function. Acts both as a chromatin remodeler and transcription coregulator. Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes expression through chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription.

Subunit / interactions. Interacts with CREBBP and EP300. May be part of a complex containing SRCAP, CREBBP, CARM1 and GRIP1. Component of the chromatin-remodeling SRCAP complex composed of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, VPS72, ACTR6 and ZNHIT1. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. (Microbial infection) Interacts with hepatitis C virus (HCV) NS5A. (Microbial infection) Interacts with human adenovirus 2 DBP.

Subcellular location. Nucleus.

Disease relevance. Floating-Harbor syndrome (FLHS) [MIM:136140] A rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. The disease is caused by variants affecting the gene represented in this entry. Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (DEHMBA) [MIM:619595] An autosomal dominant disorder characterized by developmental delay, speech delay, mild to severe intellectual disability, hypotonia, musculoskeletal features, and behavioral abnormalities including autistic features. Skeletal anomalies include joint hypermobility, chronic musculoskeletal pain, scoliosis, and pectus defects. Affected individuals also have non-specific and variable dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SNF2/RAD54 helicase family. SWR1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZRS2-1	1	yes
Q6ZRS2-2	2
Q6ZRS2-3	3

RefSeq proteins (1): NP_006653* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014012	HSA_dom	Domain
IPR017956	AT_hook_DNA-bd_motif	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR050520	INO80/SWR1_helicase	Family

Pfam: PF00176, PF00271, PF07529

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (77 total): compositionally biased region 39, region of interest 16, sequence variant 8, domain 3, DNA-binding region 3, sequence conflict 3, splice variant 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9UBD	X-RAY DIFFRACTION	2.53
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
9CA7	ELECTRON MICROSCOPY	3.35
9CA9	ELECTRON MICROSCOPY	3.56
9CA8	ELECTRON MICROSCOPY	3.92
9CAB	ELECTRON MICROSCOPY	3.94
6IGM	ELECTRON MICROSCOPY	4
9CAA	ELECTRON MICROSCOPY	4.04

Predicted structure (AlphaFold)

No AlphaFold model available for Q6ZRS2 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (1): 643–650

Post-translational modifications (1): 1172

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 500 (showing top): MODULE_45, MODULE_493, TGCTGAY_UNKNOWN, chr16p11, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_CHROMATIN_REMODELING, MODULE_38, TGGAAA_NFAT_Q4_01, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_INO80_TYPE_COMPLEX, GOCC_NUCLEAR_BODY, GOCC_PROTEIN_DNA_COMPLEX, GOCC_ATPASE_COMPLEX, SANSOM_APC_TARGETS, GOCC_HISTONE_DEACETYLASE_COMPLEX

GO Biological Process (9): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944), cAMP/PKA signal transduction (GO:0141156), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (12): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), catalytic activity, acting on a protein (GO:0140096), ATP-dependent chromatin remodeler activity (GO:0140658), nucleotide binding (GO:0000166), histone acetyltransferase activity (GO:0004402), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleosome (GO:0000786), Swr1 complex (GO:0000812), nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), nuclear body (GO:0016604), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of macromolecule biosynthetic process	2
ATP-dependent activity	2
catalytic activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
intracellular signaling cassette	1
cellular component organization	1
gene expression	1
macromolecule biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of macromolecule metabolic process	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription coregulator activity	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
DNA binding	1
chromatin remodeling	1
ATP-dependent activity, acting on DNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
protein-lysine-acetyltransferase activity	1
histone modifying activity	1
binding	1
chromatin	1
protein-DNA complex	1
histone deacetylase complex	1

Protein interactions and networks

STRING

2697 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRCAP	H2AZ1	P0C0S5	974
SRCAP	VPS72	Q15906	960
SRCAP	KAT5	Q92993	945
SRCAP	YEATS4	O95619	857
SRCAP	CREBBP	Q92793	850
SRCAP	RUVBL1	P82276	784
SRCAP	FLAD1	Q8NFF5	779
SRCAP	RUVBL2	Q9Y230	773
SRCAP	H2AC19	P20670	765
SRCAP	H2AC20	Q16777	765
SRCAP	ZNHIT1	O43257	761
SRCAP	G3BP1	Q13283	745
SRCAP	EP400	Q96L91	677
SRCAP	TRRAP	Q9Y4A5	662
SRCAP	H2AZ2	Q71UI9	630

IntAct

98 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
RUVBL2	ZNHIT1	psi-mi:“MI:0914”(association)	0.810
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
ZNHIT1	YEATS4	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
ACTL6A	ZNHIT1	psi-mi:“MI:0914”(association)	0.720
VPS72	ZNHIT1	psi-mi:“MI:0914”(association)	0.690
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
NFATC2IP	ZNHIT1	psi-mi:“MI:0914”(association)	0.530
YEATS4	ACTL6B	psi-mi:“MI:0914”(association)	0.530

BioGRID (192): SRCAP (Affinity Capture-MS), SRCAP (Reconstituted Complex), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Proximity Label-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS), SRCAP (Affinity Capture-MS)

ESM2 similar proteins: A0JMK9, A0JMT0, A2BIL7, A6QLA6, A8DZJ1, B2KF05, B7ZD04, O13024, O60237, O88379, O94880, P25992, P53352, Q09228, Q0IHP2, Q12495, Q12830, Q13111, Q1LVC2, Q1MTN9, Q24595, Q2PE14, Q32N93, Q3T8J9, Q52KF3, Q535K8, Q5R1T0, Q6DD45, Q6ZRS2, Q7K3L1, Q7KW09, Q7T308, Q801E2, Q803U7, Q86BP6, Q8BG95, Q8K298, Q98TA5, Q99PI5, Q9D4H9

Diamond homologs: A0A0P0WGX7, A1C9W6, A1CZE5, A2BGR3, A2R9H9, A4H7G5, A4HVU6, A4IHD2, A4PBL4, A4R227, A5E0W5, A6QQR4, A6ZL17, A6ZU34, A7EQA8, A7TJI3, A7Z019, B3LN76, B4F769, B5VE38, B6EU02, C0H4W3, C7GQI8, E7F1C4, F4HW51, O13682, O14148, P0CO16, P0CO17, P0CO18, P0CO19, P32863, P34739, P36607, P38086, P41410, P43610, P46100, P51532, P53115

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRCAP	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
SRCAP	“up-regulates activity”	AR	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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	7	64.4×	1e-09
Formation of the embryonic stem cell BAF (esBAF) complex	7	61.0×	1e-09
Formation of the polybromo-BAF (pBAF) complex	6	55.2×	3e-08
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	8	53.0×	5e-10
Regulation of endogenous retroelements	7	37.4×	3e-08
Regulation of MITF-M-dependent genes involved in pigmentation	7	26.9×	2e-07
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	6	26.1×	3e-06
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	11	18.8×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	8	60.6×	1e-10
regulation of DNA strand elongation	5	59.2×	6e-07
regulation of nucleotide-excision repair	8	54.1×	3e-10
nucleosome disassembly	6	54.1×	6e-08
regulation of double-strand break repair	7	45.7×	1e-08
regulation of mitotic metaphase/anaphase transition	8	44.5×	9e-10
positive regulation of T cell differentiation	7	35.8×	5e-08
positive regulation of stem cell population maintenance	8	30.9×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

2440 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	60
Uncertain significance	1364
Likely benign	697
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1187407	NM_006662.3(SRCAP):c.7394del (p.Pro2465fs)	Pathogenic
1320326	NM_006662.3(SRCAP):c.7218dup (p.Gln2407fs)	Pathogenic
1335964	NM_006662.3(SRCAP):c.7382del (p.Pro2461fs)	Pathogenic
1383995	NM_006662.3(SRCAP):c.7243dup (p.Ile2415fs)	Pathogenic
144049	NM_006662.3(SRCAP):c.7000C>T (p.Gln2334Ter)	Pathogenic
1675184	NM_006662.3(SRCAP):c.7864C>T (p.Gln2622Ter)	Pathogenic
1711404	NM_006662.3(SRCAP):c.5691_5695del (p.Ser1898fs)	Pathogenic
1992341	NM_006662.3(SRCAP):c.5690_5697del (p.Arg1897fs)	Pathogenic
2000537	NM_006662.3(SRCAP):c.7220_7221del (p.Gln2407fs)	Pathogenic
2024129	NM_006662.3(SRCAP):c.7372del (p.Val2458fs)	Pathogenic
2024360	NM_006662.3(SRCAP):c.7387del (p.Ser2463fs)	Pathogenic
2099559	NM_006662.3(SRCAP):c.577C>T (p.Arg193Ter)	Pathogenic
2497991	NM_006662.3(SRCAP):c.7262dup (p.Ser2422fs)	Pathogenic
2664695	NM_006662.3(SRCAP):c.7215_7216del (p.Glu2405fs)	Pathogenic
2702680	NM_006662.3(SRCAP):c.7282dup (p.Arg2428fs)	Pathogenic
280616	NM_006662.3(SRCAP):c.833del (p.Pro278fs)	Pathogenic
2831337	NM_006662.3(SRCAP):c.8270_8271del (p.Val2757fs)	Pathogenic
3024229	NM_006662.3(SRCAP):c.1319del	Pathogenic
30908	NM_006662.3(SRCAP):c.7330C>T (p.Arg2444Ter)	Pathogenic
30910	NM_006662.3(SRCAP):c.7549del (p.Gln2517fs)	Pathogenic
3169835	NM_006662.3(SRCAP):c.1358dup (p.Ala454fs)	Pathogenic
3340716	NM_006662.3(SRCAP):c.7245_7246del (p.Ser2416fs)	Pathogenic
3358948	NM_006662.3(SRCAP):c.2298_2300+3del	Pathogenic
3644038	NM_006662.3(SRCAP):c.9223G>T (p.Gly3075Ter)	Pathogenic
3659454	NM_006662.3(SRCAP):c.7420del (p.Pro2473_Ile2474insTer)	Pathogenic
3726522	NM_006662.3(SRCAP):c.4029del (p.Pro1344fs)	Pathogenic
3899467	NM_006662.3(SRCAP):c.7885G>T (p.Glu2629Ter)	Pathogenic
39978	NM_006662.3(SRCAP):c.7863dup (p.Gln2622fs)	Pathogenic
4174646	NM_006662.3(SRCAP):c.1701_1704dup (p.Gly569fs)	Pathogenic
427015	NM_006662.3(SRCAP):c.8242C>T (p.Arg2748Ter)	Pathogenic

SpliceAI

5011 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30700763:G:GG	donor_gain	1.0000
16:30700814:G:GT	donor_gain	1.0000
16:30700891:G:T	donor_gain	1.0000
16:30704061:TA:T	acceptor_loss	1.0000
16:30704062:AGAT:A	acceptor_gain	1.0000
16:30704063:GAT:G	acceptor_gain	1.0000
16:30704063:GATG:G	acceptor_gain	1.0000
16:30704311:AGCAT:A	donor_gain	1.0000
16:30704312:GCAT:G	donor_gain	1.0000
16:30704312:GCATG:G	donor_gain	1.0000
16:30704313:CAT:C	donor_gain	1.0000
16:30704314:AT:A	donor_gain	1.0000
16:30704315:TG:T	donor_loss	1.0000
16:30704316:G:GA	donor_loss	1.0000
16:30704316:G:GG	donor_gain	1.0000
16:30704316:GTAC:G	donor_loss	1.0000
16:30707177:GATTA:G	acceptor_loss	1.0000
16:30707180:TAG:T	acceptor_loss	1.0000
16:30707366:AAGG:A	donor_loss	1.0000
16:30707368:GG:G	donor_loss	1.0000
16:30707369:GTA:G	donor_loss	1.0000
16:30707369:GTAG:G	donor_loss	1.0000
16:30707370:T:G	donor_loss	1.0000
16:30707562:A:AG	acceptor_gain	1.0000
16:30707567:CACAG:C	acceptor_loss	1.0000
16:30707568:ACAG:A	acceptor_gain	1.0000
16:30707569:C:G	acceptor_gain	1.0000
16:30707570:A:AG	acceptor_gain	1.0000
16:30707570:A:AT	acceptor_loss	1.0000
16:30707570:AG:A	acceptor_gain	1.0000

AlphaMissense

20451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30704307:G:C	A100P	1.000
16:30704308:C:A	A100D	1.000
16:30707186:G:C	A104P	1.000
16:30707202:G:C	R109P	1.000
16:30707214:T:C	L113P	1.000
16:30707231:T:A	W119R	1.000
16:30707231:T:C	W119R	1.000
16:30707307:T:G	M144R	1.000
16:30707312:T:A	W146R	1.000
16:30707312:T:C	W146R	1.000
16:30707314:G:C	W146C	1.000
16:30707314:G:T	W146C	1.000
16:30707316:T:C	L147P	1.000
16:30707318:T:C	S148P	1.000
16:30707324:G:C	D150H	1.000
16:30707327:T:C	F151L	1.000
16:30707328:T:C	F151S	1.000
16:30707328:T:G	F151C	1.000
16:30707329:T:A	F151L	1.000
16:30707329:T:G	F151L	1.000
16:30707336:G:A	E154K	1.000
16:30707339:C:A	R155S	1.000
16:30707340:G:C	R155P	1.000
16:30707343:G:C	R156P	1.000
16:30707345:T:A	W157R	1.000
16:30707345:T:C	W157R	1.000
16:30707347:G:C	W157C	1.000
16:30707347:G:T	W157C	1.000
16:30707348:A:G	K158E	1.000
16:30707349:A:C	K158T	1.000

dbSNP variants (sampled 300 via entrez): RS1000033817 (16:30719318 G>A,C), RS1000086610 (16:30702655 C>G), RS1000161666 (16:30725322 C>A), RS1000317907 (16:30698967 A>G), RS1000355707 (16:30734381 C>T), RS1000393450 (16:30727713 A>C,G), RS1000522641 (16:30721824 A>G), RS1000578649 (16:30708514 CT>C), RS1000688615 (16:30737406 G>A), RS1000757722 (16:30708563 T>C), RS1000799543 (16:30715967 T>A,C,G), RS1000829552 (16:30727916 G>A), RS1000900165 (16:30708757 A>G), RS1000970918 (16:30715330 C>T), RS1001037243 (16:30720549 GCTTT>G)

Disease associations

OMIM: gene MIM:611421 | disease phenotypes: MIM:136140, MIM:619595

GenCC curated gene-disease

Disease	Classification	Inheritance
Floating-Harbor syndrome	Definitive	Autosomal dominant
developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Floating-Harbor syndrome	Definitive	AD

Mondo (12): Floating-Harbor syndrome (MONDO:0007621), developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (MONDO:0859202), autism spectrum disorder (MONDO:0005258), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), 46 XY differences of sex development (MONDO:0020040), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), non-syndromic intellectual disability (MONDO:0000509), epilepsy (MONDO:0005027), congenital heart disease (MONDO:0005453), cleft lip/palate (MONDO:0016044), microcephaly (MONDO:0001149)

Orphanet (7): Floating-Harbor syndrome (Orphanet:2044), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), 46,XY difference of sex development (Orphanet:98085), Cleft lip/palate (Orphanet:199306), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

129 total (30 of 129 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000104	Renal agenesis
HP:0000107	Renal cyst
HP:0000113	Polycystic kidney dysplasia
HP:0000121	Nephrocalcinosis
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000327	Hypoplasia of the maxilla
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004028_8	Immunoglobulin light chain (AL) amyloidosis	4.000000e-06
GCST005752_10	Systemic lupus erythematosus	2.000000e-06
GCST007269_290	Pulse pressure	1.000000e-11
GCST012396_10	Multiple myeloma	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D004827	Epilepsy	C10.228.140.490
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
C537062	Floating-harbor syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Smoke	decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Ribonucleotides	affects binding	1
Silicon Dioxide	increases expression	1
Urethane	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

7 cell lines: 4 induced pluripotent stem cell, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1TF	SHETi001-A	Induced pluripotent stem cell	Male
CVCL_A1XF	UMGWi001-B	Induced pluripotent stem cell	Male
CVCL_A6R5	SEES3-1V human SRCAP, clone1	Embryonic stem cell	Male
CVCL_A6R6	SEES3-1V human SRCAP, clone2	Embryonic stem cell	Male
CVCL_A6R7	SEES3-1V human SRCAP, clone3	Embryonic stem cell	Male
CVCL_D6KV	MHHi001-A-12	Induced pluripotent stem cell	Female
CVCL_D6KW	MHHi001-A-13	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder