SRCAP

Snf2 related CREBBP activator protein, the group of Small nucleolar RNA protein coding host genes|SRCAP complex

Basic information

Region (hg38): 16:30698209-30741409

Links

ENSG00000080603 ∙ NCBI:10847 ∙ OMIM:611421 ∙ HGNC:16974 ∙ Uniprot:Q6ZRS2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Floating-Harbor syndrome (Definitive), mode of inheritance: AD
• Floating-Harbor syndrome (Supportive), mode of inheritance: AD
• Floating-Harbor syndrome (Definitive), mode of inheritance: AD
• developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (Definitive), mode of inheritance: AD
• developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (Strong), mode of inheritance: AD
• Floating-Harbor syndrome (Strong), mode of inheritance: AD
• Floating-Harbor syndrome (Definitive), mode of inheritance: AD
• developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Floating-Harbor syndrome; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	7588969; 16523514; 20358590; 22265015; 23763483; 33909990

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRCAP gene.

• not_provided (1600 variants)
• Floating-Harbor_syndrome (502 variants)
• Developmental_delay,_hypotonia,_musculoskeletal_defects,_and_behavioral_abnormalities (468 variants)
• Inborn_genetic_diseases (390 variants)
• not_specified (108 variants)
• SRCAP-related_disorder (85 variants)
• Neurodevelopmental_disorder (31 variants)
• Intellectual_disability (5 variants)
• See_cases (5 variants)
• Autism_spectrum_disorder (2 variants)
• Microcephaly (2 variants)
• Intellectual_disability,_moderate (1 variants)
• Congenital_heart_disease (1 variants)
• Epilepsy (1 variants)
• Cleft_lip/palate (1 variants)
• 46,XY_disorder_of_sex_development (1 variants)
• Neurodevelopmental_delay (1 variants)
• Developmental_delay (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Non-syndromic_intellectual_disability (1 variants)
• Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRCAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006662.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			17	458	11	486
missense		7	1127	175	4	1313
nonsense	15	18	6			39
start loss						0
frameshift	26	35	7			68
splice donor/acceptor (+/-2bp)	1	6	4			11
Total	42	66	1161	633	15

Highest pathogenic variant AF is 0.000185915

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRCAP	protein_coding	protein_coding	ENST00000262518	32	46073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.73e-16	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.13	1634	1.89e+3	0.862	0.000118	20343
Missense in Polyphen		147	225.75	0.65117		2176
Synonymous	-3.11	850	742	1.15	0.0000419	7482
Loss of Function	9.81	6	124	0.0485	0.00000754	1310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000709	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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 by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription. {ECO:0000269|PubMed:10347196, ECO:0000269|PubMed:11522779, ECO:0000269|PubMed:14500758, ECO:0000269|PubMed:16024792, ECO:0000269|PubMed:16634648, ECO:0000269|PubMed:17617668}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:22265015}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways Affected in Adenoid Cystic Carcinoma (Consensus)

Recessive Scores

• pRec: 0.0771

Intolerance Scores

• loftool: 0.00579
• rvis_EVS: -4.14
• rvis_percentile_EVS: 0.15

Haploinsufficiency Scores

• pHI: 0.405
• hipred: Y
• hipred_score: 0.630
• ghis: 0.626

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srcap

Gene ontology

• Biological process: chromatin remodeling;regulation of transcription by RNA polymerase II;viral process;gene silencing;histone acetylation;ATP-dependent chromatin remodeling;histone exchange;positive regulation of nucleic acid-templated transcription
• Cellular component: Swr1 complex;nucleus;nucleoplasm;Golgi apparatus;nuclear body;protein-containing complex;perinuclear region of cytoplasm
• Molecular function: DNA binding;transcription coactivator activity;helicase activity;histone acetyltransferase activity;protein binding;ATP binding;ATPase activity;histone binding