GeneBe

GSC

protein-coding

goosecoid homeobox, the group of PRD class homeoboxes and pseudogenes

Gene summary

This gene encodes a member of the bicoid subfamily of the paired (PRD) homeobox family of proteins. The encoded protein acts as a transcription factor and may be autoregulatory. A similar protein in mice plays a role in craniofacial and rib cage development during embryogenesis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_173849.3

Inheritance

AR

ClinVar variants

P:4U:60B:45

Top phenotype

Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities (SAMS)

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr14:94,768,223-94,770,113

External References & Databases

Ensembl (ENSG00000133937)NCBI Gene (145258)OMIM (138890)HGNC:4612GenCCUniProt (P56915)AlphaFoldClinVar (GSC)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~1.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011227

Submitter: PanelApp Australia

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011227

Submitter: G2P

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011227

Submitter: Orphanet

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011227

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities (SAMS)AR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 9475592; 24290375Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GSC variants in ClinVar

6 Conditions Cataloged
not providedTotal: 78
not specifiedTotal: 42
Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndromeTotal: 5
GSC-related disorderTotal: 3
GSC-related disordersTotal: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173849.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
41
clinvar
3
clinvar
 45
missense
58
clinvar
1
clinvar
 59
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total3160414109
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_173849.3RefSeqNP_776248.13MANE Select
ENST00000238558.5EnsemblENSP00000238558.33MANE Select
ENST00001138026.1EnsemblENSP00000802179.13Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gscDanio rerio

Structure: head

Quality: truncated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

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

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

Cellular Component

  • nucleus
  • transcription factor complex
  • nuclear body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000238558
Coding exons
3
Length
2010
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
5
Defined
125746
p
0.0000199
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.917821090.7530.000005461600
Missense (PolyPhen)3648.4630.74283642
Synonymous-1.046050.61.190.00000267523
Loss of Function1.3348.100.4943.54e-7107

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.00000880.0000088rare
South Asian0.0000980.000098rare
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.219

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.911

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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