ITM2A

protein-coding

integral membrane protein 2A, the group of BRICHOS domain containing

Gene summary

This gene encodes a type II membrane protein that belongs to the ITM2 family. Studies in mouse suggest that it may be involved in osteo- and chondrogenic differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

MANE transcript

NM_004867.5

Inheritance

—

ClinVar variants

U:68B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chrX:79,360,384-79,367,667

External References & Databases

Ensembl (ENSG00000078596)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 kb

Loading mutation effect viewer...

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 ITM2A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004867.5. 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			9 clinvar	1 clinvar	1 clinvar	11
missense			49 clinvar	1 clinvar		50
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	68	2	1	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004867.5	RefSeq	NP_004858.1	6	MANE Select
ENST00000373298.7	Ensembl	ENSP00000362395.2	6	MANE Select
NM_001171581.2	RefSeq	NP_001165052.1	5	Standard
ENST00000434584.2	Ensembl	ENSP00000415533.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

plasma cell differentiation
immunoglobulin production
negative regulation of amyloid precursor protein biosynthetic process

Molecular Function

amyloid-beta binding
protein binding

Cellular Component

Golgi apparatus
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373298
Coding exons: 6
Length: 7284
Individuals with no LoFs: 125698
Homozygous LoFs: 1
Heterozygous LoFs: 4
Defined: 125703
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.134	94	97.7	0.962	0.00000743	1718
Missense (PolyPhen)		9	20.943	0.42973		462
Synonymous	-0.935	39	32.2	1.21	0.00000213	519
Loss of Function	1.69	2	6.75	0.296	4.78e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000073	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.266
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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