PHF20L1

Chr 8

PHD finger protein 20 like 1

Also known as: CGI-72, TDRD20B, URLC1

NCBI Gene: 51105 ENSG00000129292 UniProt: A8MW92 OMIM: 620050

The PHF20L1 protein binds methylated proteins and negatively regulates their proteasomal degradation, including key regulators like DNMT1 and SOX2. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.187). This gene is associated with neurodevelopmental disorders affecting cognitive function and early development.

OMIM ResearchSummary from RefSeq, UniProt

Enables methylation-dependent protein binding activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleoplasm. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— PHF20L1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

87 VUS of 119 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.33

OE 0.09 (0.04–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.85Z-score

OE missense 0.78 (0.72–0.84)

418 obs / 538.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.19)

0≤0.351.4

Missense OE?0.78 (0.72–0.84)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 5 / 56.3Missense obs/exp: 418 / 538.5Syn Z: -0.10

This gene — mechanism propensity

0.3196th %ile

GOF

0.2995th %ile

LOF

0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

VUS87

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	87	0	87
Likely Benign	2	0	2
Benign	0	1	1
Total	89	1	90

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

View in ClinVar →

54 pathogenic / likely-pathogenic (of 63) ClinVar copy-number / structural variants overlap PHF20L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →