MPZL1

Chr 1

myelin protein zero like 1

Also known as: MPZL1b, PZR, PZR1b, PZRa, PZRb

NCBI Gene: 9019 ENSG00000197965 UniProt: O95297 OMIM: 604376

MPZL1 encodes a cell surface receptor that mediates signal transduction by recruiting protein tyrosine phosphatases and interacting with Src family kinases, and regulates integrin-mediated cell motility. The gene has relatively low constraint to loss-of-function variants (pLI 0.16, LOEUF 0.75), but specific disease associations and inheritance patterns have not been established in the provided data. Further clinical characterization is needed to define the phenotypic spectrum associated with MPZL1 variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway and cell-cell signaling. Predicted to act upstream of or within positive regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.159

Z-score 2.12

OE 0.29 (0.13–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.06Z-score

OE missense 0.74 (0.63–0.88)

101 obs / 135.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.13–0.75)

0≤0.351.4

Missense OE?0.74 (0.63–0.88)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 3 / 10.4Missense obs/exp: 101 / 135.8Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in MPZL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

313 rare PASS variants

Rare truncating (LoF)

1 in 5,000

46 rare PASS variants

Rare synonymous (reference)

1 in 690

144 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MPZL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 5,600
South Asian	~43k	1 in 340	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 190	1 in 6,000
European (Finnish)	~27k	1 in 510	1 in 5,300
Admixed American	~22k	1 in 260	1 in 1,800
African / African American	~21k	1 in 260	1 in 3,500
East Asian	~20k	1 in 260	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 310	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓