TM2D1

protein-coding

TM2 domain containing 1

Gene summary

The protein encoded by this gene is a beta-amyloid peptide-binding protein. It contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily and known to be important in heterotrimeric G protein activation. Beta-amyloid peptide has been established to be a causative factor in neuron death and the consequent diminution of cognitive abilities observed in Alzheimer's disease. This protein may be a target of neurotoxic beta-amyloid peptide, and may mediate cellular vulnerability to beta-amyloid peptide toxicity through a G protein-regulated program of cell death. Several transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

MANE transcript

NM_032027.3

Inheritance

—

ClinVar variants

U:34

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr1:61,681,046-61,725,423

External References & Databases

Ensembl (ENSG00000162604)

Transcript & Mutation Effects

hg38 • Region Span ~44.4 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 TM2D1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 31

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032027.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			32 clinvar			32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	34	0	0	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 62 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032027.3	RefSeq	NP_114416.1	6	MANE Select
ENST00000606498.5	Ensembl	ENSP00000475700.1	6	MANE Select
ENST00000371177.2	Ensembl	ENSP00000475297.1	5	Standard
ENST00000371180.7	Ensembl	ENSP00000360222.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G protein-coupled receptor signaling pathway
apoptotic signaling pathway

Molecular Function

amyloid-beta binding
G protein-coupled receptor activity

Cellular Component

nucleoplasm
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371180
Coding exons: 6
Length: 44378
Individuals with no LoFs: 124608
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 124618
p: 0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.128	132	136	0.969	0.00000641	1701
Missense (PolyPhen)		31	47.807	0.64844		640
Synonymous	-0.337	59	55.8	1.06	0.00000270	554
Loss of Function	1.27	8	12.9	0.618	6.99e-7	155

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in amyloid-beta-induced apoptosis via its interaction with beta-APP42. {ECO:0000269|PubMed:11278849, ECO:0000269|PubMed:12836168}.;

Recessive Scores

pRec: 0.0989

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.00420

Gene Damage Prediction

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