TRHDE

protein-coding

thyrotropin releasing hormone degrading enzyme, the group of M1 metallopeptidases

Gene summary

This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008]

MANE transcript

NM_013381.3

Inheritance

—

ClinVar variants

U:114B:4

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr12:72,087,266-72,670,758

External References & Databases

Ensembl (ENSG00000072657)

Transcript & Mutation Effects

hg38 • Region Span ~583.5 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 TRHDE variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 4

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013381.3. 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			1 clinvar	1 clinvar	2 clinvar	4
missense			107 clinvar	1 clinvar		108
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	114	2	2	118

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013381.3	RefSeq	NP_037513.2	19	MANE Select
ENST00000261180.10	Ensembl	ENSP00000261180.5	19	MANE Select
ENST00000547300.2	Ensembl	ENSP00000447822.2	5	Standard
ENST00001138884.1	Ensembl	ENSP00000803097.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
signal transduction
cell-cell signaling
peptide catabolic process

Molecular Function

aminopeptidase activity
zinc ion binding
peptide binding
metalloaminopeptidase activity

Cellular Component

cytoplasm
plasma membrane
integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261180
Coding exons: 19
Length: 578377
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.79	360	543	0.663	0.0000257	6642
Missense (PolyPhen)		98	185.91	0.52714		2321
Synonymous	1.35	193	218	0.884	0.0000112	1983
Loss of Function	4.19	20	52.9	0.378	0.00000275	615

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00034	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Specific inactivation of TRH after its release.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.565
RVIS EVS: -0.93
RVIS percentile EVS: 9.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.341

Gene Damage Prediction

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