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

Predicted to enable structural molecule activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway and cell-cell signaling. Located in cell surface and focal adhesion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.75

Clinical Summary— MPZL1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

31 VUS of 44 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.75top 25%

GOF

0.7029th %ile

LOF

0.3356th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign1

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	30	1	0	31
Likely Benign	1	0	0	1
Benign	0	0	2	2
Total	31	1	2	34

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap MPZL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →