AFF3

Chr 2AD

ALF transcription elongation factor 3

Also known as: KINS, LAF4, MLLT2-like

NCBI Gene: 3899ENSG00000144218UniProt: P51826OMIM: 601464

AFF3 encodes a nuclear transcriptional activator that binds double-stranded DNA and functions in lymphoid development. Mutations cause KINSSHIP syndrome, an autosomal dominant disorder. This gene is highly constrained against loss-of-function mutations (pLI = 1.0, LOEUF = 0.22), indicating intolerance to protein-truncating variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.221 OMIM phenotype
Clinical Summary— AFF3
⚡
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.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 220 VUS of 342 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 6.30
OE 0.12 (0.07–0.22)
Highly constrained

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

Missense Constraint
1.71Z-score
OE missense 0.82 (0.77–0.88)
607 obs / 737.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.07–0.22)
0≤0.351.4
Missense OE0.82 (0.77–0.88)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 7 / 59.4Missense obs/exp: 607 / 737.9Syn Z: 0.23
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAFF3-related KINSSHIP syndromeOTHERAD
moderateAFF3-related intellectual disabilityOTHERAD
DN
0.2698th %ile
GOF
0.2597th %ile
LOF
0.85top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.22

Literature Evidence

LOFHaploinsufficiency for LAF4/AFF3 is associated with limb, brain and urogenital malformations and specific changes of the tibia that are part of the NS spectrum.PMID:18616733

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

342 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic10
VUS220
Likely Benign52
Benign15
Conflicting6
18
Pathogenic
10
Likely Pathogenic
220
VUS
52
Likely Benign
15
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
12
0
18
Likely Pathogenic
3
3
4
0
10
VUS
9
197
13
1
220
Likely Benign
0
13
6
33
52
Benign
2
3
2
8
15
Conflicting
—6
Total142223742321

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

View in ClinVar →

Protein Context — Lollipop Plot

AFF3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients