AFF2

Protein identityUniProt · HPA

UniProt accession

P51816

Gene

AFF2

Ensembl

ENSG00000155966

Chromosome

X

Canonical length

1311 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

1311 residues, UniProt reviewed canonical sequence.

>P51816|AFF2
     1  MDLFDFFRDW DLEQQCHYEQ DRSALKKREW ERRNQEVQQE DDLFSSGFDL FGEPYKVAEY
    61  TNKGDALANR VQNTLGNYDE MKNLLTNHSN QNHLVGIPKN SVPQNPNNKN EPSFFPEQKN
   121  RIIPPHQDNT HPSAPMPPPS VVILNSTLIH SNRKSKPEWS RDSHNPSTVL ASQASGQPNK
   181  MQTLTQDQSQ AKLEDFFVYP AEQPQIGEVE ESNPSAKEDS NPNSSGEDAF KEIFQSNSPE
   241  ESEFAVQAPG SPLVASSLLA PSSGLSVQNF PPGLYCKTSM GQQKPTAYVR PMDGQDQAPD
   301  ISPTLKPSIE FENSFGNLSF GTLLDGKPSA ASSKTKLPKF TILQTSEVSL PSDPSCVEEI
   361  LREMTHSWPT PLTSMHTAGH SEQSTFSIPG QESQHLTPGF TLQKWNDPTT RASTKSVSFK
   421  SMLEDDLKLS SDEDDLEPVK TLTTQCTATE LYQAVEKAKP RNNPVNPPLA TPQPPPAVQA
   481  SGGSGSSSES ESSSESDSDT ESSTTDSESN EAPRVATPEP EPPSTNKWQL DKWLNKVTSQ
   541  NKSFICGQNE TPMETISLPP PIIQPMEVQM KVKTNASQVP AEPKERPLLS LIREKARPRP
   601  TQKIPETKAL KHKLSTTSET VSQRTIGKKQ PKKVEKNTST DEFTWPKPNI TSSTPKEKES
   661  VELHDPPRGR NKATAHKPAP RKEPRPNIPL APEKKKYRGP GKIVPKSREF IETDSSTSDS
   721  NTDQEETLQI KVLPPCIISG GNTAKSKEIC GASLTLSTLM SSSGSNNNLS ISNEEPTFSP
   781  IPVMQTEILS PLRDHENLKN LWVKIDLDLL SRVPGHSSLH AAPAKPDHKE TATKPKRQTA
   841  VTAVEKPAPK GKRKHKPIEV AEKIPEKKQR LEEATTICLL PPCISPAPPH KPPNTRENNS
   901  SRRANRRKEE KLFPPPLSPL PEDPPRRRNV SGNNGPFGQD KNIAMTGQIT STKPKRTEGK
   961  FCATFKGISV NEGDTPKKAS SATITVTNTA IATATVTATA IVTTTVTATA TATATTTTTT
  1021  TTISTITSTI TTGLMDSSHL EMTSWAALPL LSSSSTNVRR PKLTFDDSVH NADYYMQEAK
  1081  KLKHKADALF EKFGKAVNYA DAALSFTECG NAMERDPLEA KSPYTMYSET VELLRYAMRL
  1141  KNFASPLASD GDKKLAVLCY RCLSLLYLRM FKLKKDHAMK YSRSLMEYFK QNASKVAQIP
  1201  SPWVSNGKNT PSPVSLNNVS PINAMGNCNN GPVTIPQRIH HMAASHVNIT SNVLRGYEHW
  1261  DMADKLTREN KEFFGDLDTL MGPLTQHSSM TNLVRYVRQG LCWLRIDAHL L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AFF2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.62

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AFF2.

Disease | AllUniProt

Conditions AFF2 is implicated in, by any mechanism.

• Intellectual developmental disorder, X-linked 109 (XLID109) MIM:309548

Disease | GeneticClinVar

18 pathogenic / likely-pathogenic of 571 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• FRAXE
• Inborn genetic diseases
• Intellectual disability
• Premature ovarian failure
• Thyroid cancer, nonmedullary, 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

1

gnomAD missense Z

1.41

DepMap mean gene effect

0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• learning or memory
• mRNA processing
• negative regulation of gene expression
• nuclear speck organization
• regulation of gene expression
• regulation of RNA splicing
• RNA splicing

Molecular functions

• G-quadruplex RNA binding

Cellular components

• nuclear speck

Protein domainsUniProt · Pfam · InterPro

• AF4/FMR2 family
• AF4 interaction motif
• AF4/FMR2, C-terminal homology domain
• AF-4 proto-oncoprotein N-terminal region
• AF4 interaction motif
• AFF4, C-terminal homology domain

KeywordsUniProt

• Intellectual disability
• mRNA processing
• mRNA splicing
• Nucleus
• Phosphoprotein
• RNA-binding
• Triplet repeat expansion