PM20D1

protein-coding

peptidase M20 domain containing 1, the group of M20 metallopeptidases

Gene summary

Enables hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides. Involved in amino acid metabolic process and lipid metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_152491.5

Inheritance

—

ClinVar variants

U:78B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr1:205,828,025-205,850,132

External References & Databases

Ensembl (ENSG00000162877)

Transcript & Mutation Effects

hg38 • Region Span ~22.1 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 PM20D1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152491.5. 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			1 clinvar	2 clinvar		3
missense			77 clinvar	7 clinvar	1 clinvar	85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	78	9	1	88

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152491.5	RefSeq	NP_689704.4	13	MANE Select
ENST00000367136.5	Ensembl	ENSP00000356104.4	13	MANE Select
ENST00001042183.1	Ensembl	ENSP00000712000.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
cellular amino acid metabolic process
nitrogen compound metabolic process
amide biosynthetic process
cellular amide catabolic process

Molecular Function

peptidase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
lyase activity
metal ion binding

Cellular Component

extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367136
Coding exons: 13
Length: 22111
Individuals with no LoFs: 125637
Homozygous LoFs: 1
Heterozygous LoFs: 110
Defined: 125748
p: 0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.417	266	286	0.931	0.0000158	3265
Missense (PolyPhen)		73	74.372	0.98155		914
Synonymous	-0.0747	120	119	1.01	0.00000731	1012
Loss of Function	-0.0642	27	26.6	1.01	0.00000148	279

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00054	0.00049	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00037	0.00037	rare
South Asian	0.00093	0.00091	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Bidirectional N-fatty-acyl amino acid synthase/hydrolase that regulates the production of N-fatty-acyl amino acids. These metabolites are endogenous chemical uncouplers of mitochondrial respiration. In an UCP1-independent manner, maybe through interaction with mitochondrial transporters, they promote proton leakage into the mitochondrial matrix. Thereby, this secreted protein may indirectly regulate the bodily dissipation of chemical energy as heat through thermogenic respiration. {ECO:0000269|PubMed:27374330}.;

Recessive Scores

pRec: 0.0669

Intolerance Scores

LoFtool: 0.944
RVIS EVS: 1.33
RVIS percentile EVS: 94.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.233

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High