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

ENSG00000080603NCBI:10847OMIM:611421HGNC:16974Uniprot:Q6ZRS2AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Floating-Harbor syndrome; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalitiesADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Genitourinary; Musculoskeletal; Neurologic7588969; 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.

EffectPLPVUSLBBSum
synonymous
17
clinvar
458
clinvar
11
clinvar
486
missense
7
clinvar
1127
clinvar
175
clinvar
4
clinvar
1313
nonsense
15
clinvar
18
clinvar
6
clinvar
39
start loss
0
frameshift
26
clinvar
35
clinvar
7
clinvar
68
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
4
clinvar
11
Total 42 66 1161 633 15

Highest pathogenic variant AF is 0.000185915

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SRCAPprotein_codingprotein_codingENST00000262518 3246073
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.002.73e-161257320161257480.0000636
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.1316341.89e+30.8620.00011820343
Missense in Polyphen147225.750.651172176
Synonymous-3.118507421.150.00004197482
Loss of Function9.8161240.04850.000007541310

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001850.000185
Ashkenazi Jewish0.0001990.000198
East Asian0.000.00
Finnish0.00004640.0000462
European (Non-Finnish)0.00007090.0000615
Middle Eastern0.000.00
South Asian0.00009810.0000980
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Srcap
Phenotype

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