GPSM2

G protein signaling modulator 2, the group of Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 1:108875349-108934545

Previous symbols: [ "DFNB82" ]

Links

ENSG00000121957 ∙ NCBI:29899 ∙ OMIM:609245 ∙ HGNC:29501 ∙ Uniprot:P81274 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Chudley-McCullough syndrome (Strong), mode of inheritance: AR
• Chudley-McCullough syndrome (Definitive), mode of inheritance: AR
• Chudley-McCullough syndrome (Strong), mode of inheritance: AR
• Chudley-McCullough syndrome (Strong), mode of inheritance: AR
• Chudley-McCullough syndrome (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• Chudley-McCullough syndrome (Supportive), mode of inheritance: AR
• Chudley-McCullough syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chudley-McCullough syndrome	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Neurologic	20602914; 20602914

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPSM2 gene.

• not provided (163 variants)
• Chudley-McCullough syndrome (83 variants)
• not specified (50 variants)
• Inborn genetic diseases (25 variants)
• Rare genetic deafness (5 variants)
• Nonsyndromic Hearing Loss, Recessive (3 variants)
• GPSM2-Related Disorders (3 variants)
• Hearing loss, autosomal recessive (2 variants)
• Hearing impairment (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPSM2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	20		25
missense			81	5		86
nonsense	4	5				9
start loss						0
frameshift	3	6	2			11
inframe indel				2		2
splice donor/acceptor (+/-2bp)	2	5	1			8
splice region	1		5	6		12
non coding			22	28	25	75
Total	9	16	111	55	25

Highest pathogenic variant AF is 0.0000592

Variants in GPSM2

This is a list of pathogenic ClinVar variants found in the GPSM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-108876991-G-C		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877008-C-G		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877024-C-T		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877036-G-C		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877048-C-T		Chudley-McCullough syndrome	Likely benign (Apr 27, 2017)
1-108877051-G-A		Chudley-McCullough syndrome	Uncertain significance (Jan 12, 2018)
1-108877080-C-G		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877108-G-A		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877120-C-T		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108877161-C-T		Chudley-McCullough syndrome	Uncertain significance (Apr 27, 2017)
1-108877171-C-A		Chudley-McCullough syndrome	Uncertain significance (Jan 12, 2018)
1-108877189-C-A		Chudley-McCullough syndrome	Uncertain significance (Mar 30, 2018)
1-108877219-C-T		Chudley-McCullough syndrome • not specified	Benign/Likely benign (Feb 11, 2020)
1-108885096-C-G			Likely benign (Aug 17, 2018)
1-108885259-T-C		not specified	Likely benign (Feb 04, 2016)
1-108885274-G-A		Chudley-McCullough syndrome	Uncertain significance (Aug 22, 2018)
1-108885278-T-A		Chudley-McCullough syndrome	Uncertain significance (Jan 13, 2018)
1-108885521-C-T		not specified	Uncertain significance (Sep 03, 2013)
1-108885533-A-T		Chudley-McCullough syndrome	Likely benign (Mar 29, 2024)
1-108885545-T-C			Uncertain significance (Sep 30, 2019)
1-108885558-T-C			Uncertain significance (Dec 28, 2022)
1-108885572-G-A			Uncertain significance (Sep 18, 2021)
1-108885627-G-A			Benign (Jun 24, 2018)
1-108885722-G-GT			Benign (Mar 29, 2019)
1-108885733-T-C			Likely benign (Oct 28, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPSM2	protein_coding	protein_coding	ENST00000406462	14	59196

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.70e-11	0.968	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	297	364	0.815	0.0000188	4515
Missense in Polyphen		106	148.89	0.71196		1783
Synonymous	1.85	101	128	0.792	0.00000645	1280
Loss of Function	2.21	22	36.4	0.605	0.00000217	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000825	0.000824
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000819	0.000818
Middle Eastern	0.00	0.00
South Asian	0.000392	0.000392
Other	0.000981	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein- dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays also an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (By similarity). {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364}.
• Pathway: Signaling by GPCR;Signal Transduction;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.293
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.69

Haploinsufficiency Scores

• pHI: 0.565
• hipred: Y
• hipred_score: 0.564
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.769

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpsm2
• Phenotype: cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: establishment of mitotic spindle orientation;mitotic spindle organization;G protein-coupled receptor signaling pathway;Ran protein signal transduction;regulation of catalytic activity;cell division;maintenance of centrosome location;regulation of mitotic spindle organization;positive regulation of protein localization to cell cortex;positive regulation of spindle assembly
• Cellular component: cytoplasm;centrosome;cytosol;cell cortex;lateral plasma membrane;protein-containing complex;mitotic spindle pole;lateral cell cortex;cell cortex region
• Molecular function: nucleotide binding;G-protein alpha-subunit binding;GDP-dissociation inhibitor activity;protein binding;protein C-terminus binding;protein domain specific binding;identical protein binding;protein self-association;dynein complex binding