ZFPL1

Chr 11

zinc finger protein like 1

Also known as: D11S750, MCG4

NCBI Gene: 7542 ENSG00000162300 UniProt: O95159 OMIM: 619397

ZFPL1 encodes a protein required for cis-Golgi integrity and efficient endoplasmic reticulum to Golgi transport, and is predicted to function as a transcriptional regulator through DNA and zinc ion binding. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity, typically presenting in infancy with developmental delays affecting the nervous system. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of DNA-templated transcription. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.009

Z-score 2.22

OE 0.39 (0.21–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.93 (0.82–1.05)

189 obs / 203.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.21–0.77)

0≤0.351.4

Missense OE?0.93 (0.82–1.05)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 6 / 15.4Missense obs/exp: 189 / 203.5Syn Z: 0.03

Background carrier burden — how many people carry a rare variant somewhere in ZFPL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

460 rare PASS variants

Rare truncating (LoF)

1 in 4,400

65 rare PASS variants

Rare synonymous (reference)

1 in 340

196 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZFPL1. 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 110	1 in 3,800
South Asian	~43k	1 in 92	1 in 4,800
Remaining (unassigned)	~30k	1 in 74	≈ 1 in 10,000
European (Finnish)	~27k	1 in 130	≈ 1 in 27,000
Admixed American	~22k	1 in 79	≈ 1 in 11,000
African / African American	~21k	1 in 76	1 in 2,100
East Asian	~20k	1 in 120	1 in 2,500
Ashkenazi Jewish	~13k	1 in 260	none seen
Middle Eastern	~2,884	1 in 93	≈ 1 in 2,900

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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓