SRGAP1

SLIT-ROBO Rho GTPase activating protein 1, the group of AH/BAR family Rho GTPase activating proteins|F-BAR domain containing

Basic information

Region (hg38): 12:63843761-64162217

Links

ENSG00000196935

∙ NCBI:57522 ∙ OMIM:606523 ∙ HGNC:17382 ∙ Uniprot:Q7Z6B7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

thyroid cancer, nonmedullary, 2 (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRGAP1 gene.

not_specified (92 variants)
not_provided (31 variants)
SRGAP1-related_disorder (20 variants)
Thyroid_cancer,_nonmedullary,_2 (8 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (3 variants)
Nephronophthisis (1 variants)
Congenital_anomalies_of_kidney_and_urinary_tract_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRGAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020762.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				16 clinvar	7 clinvar	23
missense	1 clinvar		104 clinvar	2 clinvar	2 clinvar	109
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	0	106	18	9

Highest pathogenic variant AF is 0.000007532616

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRGAP1	protein_coding	protein_coding	ENST00000355086	22	303541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00155	125729	0	17	125746	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	454	607	0.748	0.0000330	7204
Missense in Polyphen		90	150.86	0.59656		1767
Synonymous	1.39	202	229	0.883	0.0000130	2019
Loss of Function	5.81	8	54.1	0.148	0.00000293	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000719	0.0000703
Middle Eastern	0.000110	0.000109
South Asian	0.000131	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42. {ECO:0000269|PubMed:11672528}.;
Disease: DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:23539728}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Signal Transduction;Rho GTPase cycle;Inactivation of CDC42 and RAC1;Signaling by Rho GTPases;Signaling by ROBO receptors;Axon guidance;Regulation of RhoA activity (Consensus)

Recessive Scores

pRec: 0.136

Intolerance Scores

loftool: 0.610
rvis_EVS: -0.82
rvis_percentile_EVS: 12.01

Haploinsufficiency Scores

pHI: 0.370
hipred: Y
hipred_score: 0.756
ghis: 0.548

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.503

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Srgap1
Phenotype

Gene ontology

Biological process: signal transduction;negative regulation of cell migration;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
Cellular component: cytoplasm;cytosol
Molecular function: GTPase activator activity;protein binding;Rac GTPase binding