ISX

protein-coding

intestine specific homeobox, the group of PRD class homeoboxes and pseudogenes

Gene summary

Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the RAXLX homeobox gene family. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001303508.2

Inheritance

—

ClinVar variants

U:33B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr22:35,066,136-35,087,387

External References & Databases

Ensembl (ENSG00000175329)

Transcript & Mutation Effects

hg38 • Region Span ~21.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ISX variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001303508.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			33 clinvar	2 clinvar	1 clinvar	36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	2	3	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001303508.2	RefSeq	NP_001290437.1	4	MANE Select
ENST00000404699.7	Ensembl	ENSP00000386037.1	4	MANE Select
NM_001438732.1	RefSeq	NP_001425661.1	4	Standard
ENST00000308700.6	Ensembl	ENSP00000311492.6	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308700
Coding exons: 4
Length: 21252
Individuals with no LoFs: 125567
Homozygous LoFs: 0
Heterozygous LoFs: 178
Defined: 125745
p: 0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.430	152	138	1.10	0.00000760	1565
Missense (PolyPhen)		46	38.36	1.1992		413
Synonymous	-0.480	60	55.5	1.08	0.00000312	506
Loss of Function	0.203	7	7.60	0.921	4.03e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00060	0.00060	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.000065	0.000065	rare
Other	0.0016	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that regulates gene expression in intestine. May participate in vitamin A metabolism most likely by regulating BCO1 expression in the intestine (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0964

Intolerance Scores

LoFtool: 0.229
RVIS EVS: 1.26
RVIS percentile EVS: 93.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0936

Gene Damage Prediction

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