TNFRSF10A

protein-coding

TNF receptor superfamily member 10a, the group of CD molecules|Tumor necrosis factor receptor superfamily

Gene summary

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003844.4

Inheritance

—

ClinVar variants

P:1U:96B:18

Top phenotype

Primary ciliary dyskinesia

gnomAD constraint

pLI —, LoF o/e 1.08

Max pathogenic AF

—

Genomic locus

chr8:23,190,452-23,225,102

External References & Databases

Ensembl (ENSG00000104689)

Transcript & Mutation Effects

hg38 • Region Span ~34.7 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 TNFRSF10A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 16

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003844.4. 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			1 clinvar	4 clinvar	4 clinvar	9
missense			90 clinvar	8 clinvar	2 clinvar	100
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	96	12	6	115

Highest pathogenic variant AF is 0.00008877455

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003844.4	RefSeq	NP_003835.3	10	MANE Select
ENST00000221132.8	Ensembl	ENSP00000221132.3	10	MANE Select
ENST00000524158.5	Ensembl	ENSP00000428884.1	4	Standard
ENST00000613472.1	Ensembl	ENSP00000480778.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
Necroptosis - Homo sapiens (human)
Natural killer cell mediated cytotoxicity - Homo sapiens (human)
Measles - Homo sapiens (human)
Apoptosis - Homo sapiens (human)

Biological Process

apoptotic process
activation of cysteine-type endopeptidase activity involved in apoptotic process
signal transduction
cell surface receptor signaling pathway
activation of NF-kappaB-inducing kinase activity

Molecular Function

protease binding
death receptor activity
protein binding
transcription factor binding
signaling receptor activity

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221132
Coding exons: 10
Length: 34675
Individuals with no LoFs: 125580
Homozygous LoFs: 0
Heterozygous LoFs: 168
Defined: 125748
p: 0.000668

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.645	291	262	1.11	0.0000139	2984
Missense (PolyPhen)		51	44.885	1.1362		560
Synonymous	-1.06	120	106	1.13	0.00000606	954
Loss of Function	-0.342	21	19.4	1.08	9.32e-7	223

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0	0.0	absent
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:26457518). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. {ECO:0000269|PubMed:26457518, ECO:0000269|PubMed:9430227}.;

Recessive Scores

pRec: 0.0662

Intolerance Scores

LoFtool: 0.280
RVIS EVS: 0.51
RVIS percentile EVS: 80.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0357

Gene Damage Prediction

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