TM2D3

protein-coding

TM2 domain containing 3

Gene summary

The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. Several alternatively spliced transcript variants of this gene are described but the full length nature of some variants has not been determined. Multiple polyadenylation sites have been found in this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_078474.3

Inheritance

ClinVar variants

P:4U:49B:3

Top phenotype

TM2D3-related disorder

gnomAD constraint

pLI —, LoF o/e 1.07

Max pathogenic AF

—

Genomic locus

chr15:101,621,444-101,652,391

External References & Databases

Ensembl (ENSG00000184277)

Transcript & Mutation Effects

hg38 • Region Span ~30.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TM2D3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 45

TM2D3-related disorderTotal: 4

Neurocardiorenal malformation syndromeTotal: 3

not providedTotal: 2

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_078474.3. 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				2 clinvar		2
missense		2 clinvar	48 clinvar	1 clinvar		51
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	4	49	3	0	56

Highest pathogenic variant AF is 0.000011061901

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_078474.3	RefSeq	NP_510883.2	6	MANE Select
ENST00000333202.8	Ensembl	ENSP00000330433.3	6	MANE Select
NM_001307960.2	RefSeq	NP_001294889.1	5	Standard
NM_001308026.2	RefSeq	NP_001294955.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333202
Coding exons: 6
Length: 30748
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125748
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.743	174	149	1.17	0.00000824	1586
Missense (PolyPhen)		48	51.004	0.9411		527
Synonymous	-1.68	74	57.7	1.28	0.00000329	493
Loss of Function	-0.216	12	11.2	1.07	4.75e-7	135

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00036	0.00036	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.237
RVIS EVS: 0.35
RVIS percentile EVS: 74.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.359

Gene Damage Prediction

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