MMEL1

protein-coding

membrane metalloendopeptidase like 1, the group of M13 metallopeptidases

Gene summary

The protein encoded by this gene is a member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]

Previous symbols:

MMEL2

MANE transcript

NM_033467.4

Inheritance

—

ClinVar variants

U:146B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr1:2,590,639-2,633,016

External References & Databases

Ensembl (ENSG00000142606)

Transcript & Mutation Effects

hg38 • Region Span ~42.4 kb

Loading mutation effect viewer...

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 MMEL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 149

not providedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033467.4. 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			2 clinvar	7 clinvar	4 clinvar	13
missense			143 clinvar	7 clinvar	3 clinvar	153
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	146	14	7	167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033467.4	RefSeq	NP_258428.2	23	MANE Select
ENST00000378412.8	Ensembl	ENSP00000367668.3	23	MANE Select
ENST00000471840.5	Ensembl	ENSP00000461938.1	3	Standard
ENST00000502556.5	Ensembl	ENSP00000422492.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

metalloendopeptidase activity
metal ion binding

Cellular Component

extracellular region
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378412
Coding exons: 23
Length: 42404
Individuals with no LoFs: 125634
Homozygous LoFs: 1
Heterozygous LoFs: 113
Defined: 125748
p: 0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.126	480	488	0.984	0.0000318	5059
Missense (PolyPhen)		214	225.91	0.94728		2395
Synonymous	0.0965	203	205	0.991	0.0000144	1470
Loss of Function	1.57	41	53.4	0.768	0.00000300	522

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00054	0.00053	rare
South Asian	0.00062	0.00062	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.200

Intolerance Scores

LoFtool: 0.224
RVIS EVS: -0.66
RVIS percentile EVS: 16.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.137

Gene Damage Prediction

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