IGSF1

immunoglobulin superfamily member 1, the group of Immunoglobulin like domain containing

Basic information

Region (hg38): X:131273506-131578899

Links

ENSG00000147255

∙ NCBI:3547 ∙ OMIM:300137 ∙ HGNC:5948 ∙ Uniprot:Q8N6C5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

X-linked central congenital hypothyroidism with late-onset testicular enlargement (Definitive), mode of inheritance: XL
X-linked central congenital hypothyroidism with late-onset testicular enlargement (Strong), mode of inheritance: XL
X-linked central congenital hypothyroidism with late-onset testicular enlargement (Supportive), mode of inheritance: XL
X-linked central congenital hypothyroidism with late-onset testicular enlargement (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Central hypothyroidism and testicular enlargement	XL	Endocrine	Individuals can demonstrate a number of endocrine deficiencies (including central hypothyroidism, as well as growth hormone deficiency), for which hormone replacement therapy may be beneficial	Endocrine;Genitourinary; Neurologic	23143598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGSF1 gene.

not provided (5 variants)
X-linked central congenital hypothyroidism with late-onset testicular enlargement (5 variants)
Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGSF1 gene is commonly pathogenic or not. These statistics are base on transcript: . 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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2 clinvar	5 clinvar	9 clinvar	16
missense			84 clinvar	37 clinvar	6 clinvar	127
nonsense	5 clinvar	2 clinvar	1 clinvar			8
start loss						0
frameshift	2 clinvar	1 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar				3
Total	9	4	88	42	15

Highest pathogenic variant AF is 0.0000178481

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGSF1	protein_coding	protein_coding	ENST00000370903	19	126198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000726	125737	2	7	125746	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	439	512	0.857	0.0000376	8727
Missense in Polyphen		126	193.52	0.65108		3583
Synonymous	-1.05	213	194	1.10	0.0000146	2677
Loss of Function	5.83	5	49.1	0.102	0.00000388	732

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.00	0.00
Finnish	0.000125	0.0000924
European (Non-Finnish)	0.0000614	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000530	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary to mediate a specific antagonistic effect of inhibin B on activin-stimulated transcription. {ECO:0000250, ECO:0000269|PubMed:11266516}.;
Disease: DISEASE: Hypothyroidism, central, and testicular enlargement (CHTE) [MIM:300888]: A disorder characterized by insufficient thyroid gland stimulation by thyroid stimulating hormone (TSH), resulting from hypothalamic and/or pituitary dysfunction. CHTE patients have delayed testosterone increase at puberty with normal testosterone levels in adulthood, normal testicular volume in childhood and enlarged testicles in adulthood. {ECO:0000269|PubMed:23143598}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.109

Intolerance Scores

loftool: 0.379
rvis_EVS: -0.62
rvis_percentile_EVS: 17.47

Haploinsufficiency Scores

pHI: 0.603
hipred: Y
hipred_score: 0.536
ghis: 0.527

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.517

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Igsf1
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); normal phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: regulation of transcription, DNA-templated;negative regulation of activin receptor signaling pathway
Cellular component: extracellular region;membrane;integral component of membrane
Molecular function: protein binding;coreceptor activity;inhibin binding;activin receptor antagonist activity