HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
AFF4
ALF transcription elongation factor 4
Chromosome 5 Β· 5q31.1
NCBI Gene: 27125Ensembl: ENSG00000072364.14HGNC: HGNC:17869UniProt: Q9UHB7
117PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneOncogeneTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingtranscription elongation factor complexfibrillar centernuclear bodyCognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome3q26 microduplication syndromecolorectal adenocarcinomacarcinoma of liver and intrahepatic biliary tract
✦AI Summary

AFF4 (ALF transcription elongation factor 4) serves as a central scaffolding protein in the super elongation complex (SEC), which enhances RNA polymerase II transcription elongation by suppressing polymerase pausing 1. AFF4 recruits other SEC components through direct interactions with ELL proteins and the P-TEFb complex, facilitating transcriptional elongation of target genes 1. The protein plays critical roles in cellular differentiation processes, promoting osteogenic differentiation of mesenchymal stem cells through regulation of ID1 expression and BMP2 signaling 2, while also enhancing adipogenic differentiation by targeting autophagy-related genes ATG5 and ATG16L1 3. In disease contexts, AFF4 mutations cause CHOPS syndrome, a disorder of transcriptional regulation characterized by cognitive impairment and developmental abnormalities 45. AFF4 also contributes to cancer progression, particularly in lung adenocarcinoma where it promotes glycolysis and cisplatin resistance through PTEN/PI3K/AKT/mTOR pathway modulation 6. Additionally, AFF4 facilitates HIV-1 replication by forming complexes with viral Tat protein and P-TEFb, making it a potential therapeutic target 1. The protein's diverse functions highlight its importance in transcriptional control, development, and pathological processes.

Sources cited
1
AFF4 serves as scaffolding protein in SEC and facilitates HIV-1 transcription through Tat protein interaction
PMID: 24727379
2
AFF4 promotes osteogenic differentiation through ID1 regulation and BMP2 signaling
PMID: 28955517
3
AFF4 enhances adipogenic differentiation by targeting autophagy genes ATG5 and ATG16L1
PMID: 36149892
4
AFF4 mutations cause CHOPS syndrome and CdLS-like phenotypes
PMID: 37377026
5
AFF4 is associated with disorders of transcriptional regulation
PMID: 31516082
6
AFF4 promotes lung cancer progression and cisplatin resistance through PTEN/PI3K/AKT/mTOR pathway
PMID: 40790766
Disease Associationsβ“˜21
Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndromeOpen Targets
0.76Strong
3q26 microduplication syndromeOpen Targets
0.60Moderate
bile duct carcinomaOpen Targets
0.37Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
esophageal adenocarcinomaOpen Targets
0.37Weak
Hepatobiliary NeoplasmOpen Targets
0.37Weak
kidney neoplasmOpen Targets
0.37Weak
lung carcinomaOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
hepatocellular carcinomaOpen Targets
0.30Weak
head and neck squamous cell carcinomaOpen Targets
0.30Weak
lung adenocarcinomaOpen Targets
0.30Weak
melanomaOpen Targets
0.28Weak
urinary bladder carcinomaOpen Targets
0.28Weak
acute myeloid leukemiaOpen Targets
0.28Weak
pancreatic ductal adenocarcinomaOpen Targets
0.28Weak
CHOPS syndromeUniProt
Pathogenic Variants7
NM_014423.4(AFF4):c.772C>T (p.Arg258Trp)Pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 258
NM_014423.4(AFF4):c.778A>G (p.Met260Val)Likely pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 260
NM_014423.4(AFF4):c.761C>G (p.Thr254Ser)Pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 254
NM_014423.4(AFF4):c.758C>T (p.Pro253Leu)Pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 253
NM_014423.4(AFF4):c.767A>C (p.Tyr256Ser)Likely pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 256
NM_014423.4(AFF4):c.773G>C (p.Arg258Pro)Pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 258
NM_014423.4(AFF4):c.760A>G (p.Thr254Ala)Pathogenic
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
β˜†β˜†β˜†β˜†2015β†’ Residue 254
View on ClinVar β†—
Related Genes
KMT2AProtein interaction100%HEXIM1Protein interaction100%CDC73Protein interaction100%LEO1Protein interaction100%DOT1LProtein interaction100%MEPCEProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
71%
Ovary
60%
Liver
57%
Lung
50%
Heart
47%
Gene Interaction Network
Click a node to explore
AFF4KMT2AHEXIM1CDC73LEO1DOT1LMEPCE
PROTEIN STRUCTURE
Preparing viewer…
PDB5JW9 Β· 2.00 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.11Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.06 [0.03–0.11]
RankingsWhere AFF4 stands among ~20K protein-coding genes
  • #4,022of 20,598
    Most Researched117 Β· top quartile
  • #3,175of 5,498
    Most Pathogenic Variants7
  • #96of 17,882
    Most Constrained (LOEUF)0.11 Β· top 1%
Genes detectedAFF4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.
PMID: 37377026
Am J Med Genet A Β· 2023
1.00
2
The expanding phenotypes of cohesinopathies: one ring to rule them all!
PMID: 31516082
Cell Cycle Β· 2019
0.90
3
AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.
PMID: 28955517
Bone Res Β· 2017
0.80
4
The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.
PMID: 37815186
Comb Chem High Throughput Screen Β· 2024
0.70
5
Small-molecule inhibitor of AF9/ENL-DOT1L/AF4/AFF4 interactions suppresses malignant gene expression and tumor growth.
PMID: 34373735
Theranostics Β· 2021
0.60