GSC

goosecoid homeobox, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 14:94768222-94770113

Links

ENSG00000133937 ∙ NCBI:145258 ∙ OMIM:138890 ∙ HGNC:4612 ∙ Uniprot:P56915 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome (Supportive), mode of inheritance: AR
• short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities (SAMS)	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal	9475592; 24290375

ClinVar

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

• not provided (53 variants)
• Inborn genetic diseases (14 variants)
• not specified (2 variants)
• Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSC 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			1	17	6	24
missense			35		1	36
nonsense						0
start loss						0
frameshift						0
inframe indel			1	1	1	3
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				2	3	5
Total	0	0	37	20	11

Variants in GSC

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

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

Position	Type	Phenotype	Significance	ClinVar
14-94768521-T-C			Likely benign (Jan 13, 2023)
14-94768550-TCGA-T			Likely benign (Jan 08, 2024)
14-94768580-C-A		not specified	Uncertain significance (Feb 22, 2023)
14-94768614-C-A			Likely benign (Oct 13, 2023)
14-94768772-C-A			Benign (Jun 20, 2021)
14-94768949-G-A			Likely benign (Dec 06, 2022)
14-94768950-G-A			Likely benign (Dec 26, 2023)
14-94768951-C-A			Likely benign (Sep 27, 2022)
14-94768951-C-T			Likely benign (Jun 22, 2021)
14-94768967-C-G			Uncertain significance (Oct 25, 2022)
14-94768983-A-G			Uncertain significance (Sep 23, 2022)
14-94768997-CT-GG			Uncertain significance (Nov 28, 2022)
14-94769002-C-T		not specified	Uncertain significance (Aug 10, 2021)
14-94769007-G-A			Uncertain significance (Mar 28, 2022)
14-94769009-G-A			Uncertain significance (Dec 22, 2021)
14-94769018-C-T			Likely benign (Oct 25, 2021)
14-94769021-G-A			Benign (Jan 21, 2024)
14-94769026-T-G			Uncertain significance (Aug 16, 2022)
14-94769034-T-C		not specified	Uncertain significance (Dec 08, 2023)
14-94769081-G-A			Likely benign (May 16, 2022)
14-94769084-G-A			Likely benign (Nov 13, 2023)
14-94769111-C-A		not specified	Uncertain significance (Dec 07, 2021)
14-94769111-C-T			Likely benign (Oct 24, 2023)
14-94769116-T-C		not specified	Uncertain significance (May 23, 2023)
14-94769128-G-A			Likely benign (Feb 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSC	protein_coding	protein_coding	ENST00000238558	3	2010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0139	0.878	125741	0	5	125746	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.917	82	109	0.753	0.00000546	1600
Missense in Polyphen		36	48.463	0.74283		642
Synonymous	-1.04	60	50.6	1.19	0.00000267	523
Loss of Function	1.33	4	8.10	0.494	3.54e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates chordin (CHRD). May play a role in spatial programing within discrete embryonic fields or lineage compartments during organogenesis. In concert with NKX3-2, plays a role in defining the structural components of the middle ear; required for the development of the entire tympanic ring (By similarity). Probably involved in the regulatory networks that define neural crest cell fate specification and determine mesoderm cell lineages in mammals. {ECO:0000250, ECO:0000269|PubMed:24290375}.
• Disease: DISEASE: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities (SAMS) [MIM:602471]: An autosomal recessive developmental disorder with features of a first and second branchial arch syndrome, and with unique rhizomelic skeletal anomalies. Craniofacial abnormalities can lead to conductive hearing loss, respiratory insufficiency, and feeding difficulties. Skeletal features include bilateral humeral hypoplasia, humeroscapular synostosis, pelvic abnormalities, and proximal defects of the femora. Affected individuals may also have some features of a neurocristopathy or abnormal mesoderm development, such as urogenital anomalies, that are distinct from other branchial arch syndromes. {ECO:0000269|PubMed:24290375}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Developmental Biology;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Transcriptional regulation of pluripotent stem cells;Regulation of retinoblastoma protein;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.219

Haploinsufficiency Scores

• pHI: 0.204
• hipred: Y
• hipred_score: 0.766
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.911

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gsc
• Phenotype: skeleton phenotype; digestive/alimentary 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); taste/olfaction phenotype

Zebrafish Information Network

• Gene name: gsc
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: truncated

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;gastrulation;neural crest cell fate specification;dorsal/ventral neural tube patterning;signal transduction involved in regulation of gene expression;negative regulation of Wnt signaling pathway;forebrain development;middle ear morphogenesis;muscle organ morphogenesis;embryonic skeletal system morphogenesis
• Cellular component: nucleus;transcription factor complex;nuclear body
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;RNA polymerase II repressing transcription factor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific