RTRAF

gene
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Also known as CGI-99RLLM1CLECLE7LCRP369hCLE1

Summary

RTRAF (RNA transcription, translation and transport factor, HGNC:23169) is a protein-coding gene on chromosome 14q22.1, encoding tRNA-splicing ligase complex subunit RTRAF (Q9Y224). Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosphodiester. It is a selective cancer dependency (DepMap: 39.7% of cell lines).

Enables RNA binding activity; RNA polymerase II complex binding activity; and identical protein binding activity. Involved in negative regulation of protein kinase activity; positive regulation of transcription by RNA polymerase II; and tRNA splicing, via endonucleolytic cleavage and ligation. Located in microtubule cytoskeleton; nucleoplasm; and perinuclear region of cytoplasm. Part of tRNA-splicing ligase complex.

Source: NCBI Gene 51637 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 16 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 39.7% of screened cell lines
  • MANE Select transcript: NM_016039

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:23169
Approved symbolRTRAF
NameRNA transcription, translation and transport factor
Location14q22.1
Locus typegene with protein product
StatusApproved
AliasesCGI-99, RLLM1, CLE, CLE7, LCRP369, hCLE1
Ensembl geneENSG00000087302
Ensembl biotypeprotein_coding
OMIM610858
Entrez51637

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000261700, ENST00000553362, ENST00000553479, ENST00000553707, ENST00000555319, ENST00000556760, ENST00000557553, ENST00000902518, ENST00000902519, ENST00000902520, ENST00000920645, ENST00000920646, ENST00000920647, ENST00000920648, ENST00000920649, ENST00000942315

RefSeq mRNA: 1 — MANE Select: NM_016039 NM_016039

CCDS: CCDS9705

Canonical transcript exons

ENST00000261700 — 8 exons

ExonStartEnd
ENSE000006572395199131751991441
ENSE000006572455200419452004242
ENSE000008546965198954651989700
ENSE000012273815199372351993822
ENSE000013659735200436252010694
ENSE000036291135199970851999796
ENSE000036618095200179852001866
ENSE000036849285199849451998580

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 247.9264 / max 1457.4527, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
139598243.28371827
1395994.13831504
1396010.4930228
1396000.01137

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065599.82gold quality
oocyteCL:000002399.65gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099199.48gold quality
right testisUBERON:000453499.46gold quality
left testisUBERON:000453399.44gold quality
cartilage tissueUBERON:000241899.03gold quality
ganglionic eminenceUBERON:000402399.02gold quality
calcaneal tendonUBERON:000370198.99gold quality
embryoUBERON:000092298.98gold quality
palpebral conjunctivaUBERON:000181298.96gold quality
adult organismUBERON:000702398.93gold quality
heart right ventricleUBERON:000208098.89gold quality
body of pancreasUBERON:000115098.88gold quality
tibiaUBERON:000097998.84gold quality
heart left ventricleUBERON:000208498.83gold quality
cortical plateUBERON:000534398.83gold quality
cardiac ventricleUBERON:000208298.82gold quality
lower esophagus muscularis layerUBERON:003583398.82gold quality
testisUBERON:000047398.81gold quality
lower esophagusUBERON:001347398.81gold quality
esophagogastric junction muscularis propriaUBERON:003584198.74gold quality
male germ cellCL:000001598.73gold quality
esophagus squamous epitheliumUBERON:000692098.71gold quality
heartUBERON:000094898.70gold quality
body of stomachUBERON:000116198.69gold quality
right atrium auricular regionUBERON:000663198.69gold quality
muscle layer of sigmoid colonUBERON:003580598.67gold quality
spermCL:000001998.66gold quality
olfactory segment of nasal mucosaUBERON:000538698.66gold quality
right adrenal gland cortexUBERON:003582798.65gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-MTAB-10042yes4.47
E-MTAB-7606no511.52
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting RTRAF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-186-5P99.9970.833707
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-313399.8170.923506
HSA-MIR-542-3P99.3467.581270
HSA-MIR-450499.1069.141328
HSA-MIR-6770-5P98.9766.761853
HSA-MIR-3124-3P98.8768.952123
HSA-MIR-4477A98.8369.752952
HSA-MIR-390898.7567.311160
HSA-MIR-450198.7267.19921
HSA-MIR-4703-5P98.5370.131645
HSA-MIR-3942-5P98.5269.511517
HSA-MIR-216B-5P97.1666.761126
HSA-MIR-517-5P97.1368.43781

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

  • A novel protein CGI-99 is isolated, which may be involved in the functional regulation of human ninein in the centrosome structure and may also be important in brain development and tumorigenesis. (PMID:15147888)
  • c14orf166 was identified asa novel metastasis-associated protein, and the roles of radixin, moesin and c14orf166 in pancreatic cancer metastasis deserve further investigations. (PMID:19152423)
  • spatial interactions of hnRNPH1, NF45, and C14orf166 with HCVc174 likely modulate HCV or cellular functions during acute and chronic HCV infection (PMID:21823664)
  • Silencing of CLE causes reduction of influenza A virus polymerase activity, viral RNA transcription and replication, virus titer, and viral particle production. (PMID:21900157)
  • hCLE/C14orf166 associates with DDX1, HSPC117, and FAM98B in a novel transcription-dependent shuttling RNA-transporting complex. (PMID:24608264)
  • Overexpression of chromosome 14 open reading frame 166 correlates with disease progression in nasopharyngeal carcinoma. (PMID:25964093)
  • C14ORF166 may represent a biomarker of pelvic lymph node metastasis in uterine cervical cancer (PMID:26219895)
  • C14orf166, a cellular protein required for viral replication, is incorporated into influenza virus particles. (PMID:26864902)
  • C14orf166 could be a novel prognostic biomarker of breast cancer, it also contributes to cell proliferation by regulating G1/S transition. (PMID:26883017)
  • C14orf166 promotes bladder cancer cell proliferation and can be a novel prognostic biomarker for patients with bladder cancer. (PMID:26905879)
  • the two structural homologs FAM98A and FAM98B included in a novel complex with DDX1 and C14orf166 are required for PRMT1 expression in colorectal cancer cell lines (PMID:28040436)
  • Molecular architecture of the human tRNA ligase complex. (PMID:34854379)
  • An in silico prediction of interaction models of influenza A virus PA and human C14orf166 protein from yeast-two-hybrid screening data. (PMID:37265372)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriortrafENSDARG00000009253
mus_musculusRtrafENSMUSG00000021807
rattus_norvegicusRtrafENSRNOG00000000340
drosophila_melanogasterCG31249FBGN0051249
caenorhabditis_elegansWBGENE00008457

Protein

Protein identifiers

tRNA-splicing ligase complex subunit RTRAFQ9Y224 (reviewed: Q9Y224)

Alternative names: CLE7 homolog, RNA transcription, translation and transport factor protein

All UniProt accessions (5): Q9Y224, G3V4C6, G3V4E7, H0YJB9, Q549M8

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosphodiester. RNA-binding protein involved in modulation of mRNA transcription by Polymerase II. Could also play a role in RNA transport. (Microbial infection) In case of infection by influenza virus A (IVA), is involved in viral replication.

Subunit / interactions. Homodimer. Component of the tRNA-splicing ligase core complex composed of the catalytic subunit RTCB and the accessory proteins DDX1, C2orf49/Ashwin/ASW, FAM98B and RTRAF/CGI-99. Interacts with FAM98A (via N- and C-terminus). Interacts with NIN; which may prevent phosphorylation of NIN. Interacts with POLR2A. (Microbial infection) Interacts with influenza A virus (IAV) RNA polymerase subunits PA, PB1 and PB2, and nucleocapsid NP. Associates with IAV polymerase complexes both in the nucleus and cytosol. Associates with IAV ribonucleoproteins (vRNP) packaged in virions. Interacts with hepatitis C virus core protein p19.

Subcellular location. Nucleus. Cytoplasm. Cytosol. Perinuclear region. Cytoskeleton. Microtubule organizing center. Centrosome Nucleus.

Tissue specificity. Widely expressed. Expressed at high level in heart and skeletal muscle. Expressed at intermediate level in liver, pancreas, fetal brain and fetal lung. Weakly expressed in adult brain, adult lung, placenta, fetal liver and fetal kidney. Overexpressed in many brain tumors.

Induction. (Microbial infection) Up-regulated specifically following influenza A virus (IAV) infection in a viral replication-dependent manner (at protein level).

Similarity. Belongs to the RTRAF family.

RefSeq proteins (1): NP_057123* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR019265RTRAFFamily

Pfam: PF10036

UniProt features (11 total): helix 7, modified residue 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
7P3AX-RAY DIFFRACTION2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9Y224-F172.090.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 20, 62, 98

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-6784531tRNA processing in the nucleus
R-HSA-72306tRNA processing
R-HSA-8953854Metabolism of RNA

MSigDB gene sets: 159 (showing top): YAATNRNNNYNATT_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_DN

GO Biological Process (4): tRNA splicing, via endonucleolytic cleavage and ligation (GO:0006388), negative regulation of protein kinase activity (GO:0006469), positive regulation of transcription by RNA polymerase II (GO:0045944), RNA transport (GO:0050658)

GO Molecular Function (4): RNA polymerase II complex binding (GO:0000993), RNA binding (GO:0003723), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), tRNA-splicing ligase complex (GO:0072669), mitotic spindle (GO:0072686), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
tRNA processing1
Metabolism of RNA1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
cytoplasm2
RNA splicing, via endonucleolytic cleavage and ligation1
tRNA processing1
negative regulation of protein phosphorylation1
protein kinase activity1
negative regulation of kinase activity1
regulation of protein kinase activity1
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
positive regulation of DNA-templated transcription1
nucleic acid transport1
establishment of RNA localization1
RNA polymerase core enzyme binding1
nucleic acid binding1
protein binding1
binding1
intracellular membrane-bounded organelle1
nuclear lumen1
intracellular anatomical structure1
centriole1
microtubule organizing center1
intracellular protein-containing complex1
catalytic complex1
spindle1
intracellular membraneless organelle1

Protein interactions and networks

STRING

1680 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RTRAFFAM98BQ52LJ0996
RTRAFDDX1Q92499992
RTRAFRTCBQ9Y3I0943
RTRAFNINQ8N4C6907
RTRAFC2orf49Q9BVC5896
RTRAFRMDN3Q96TC7730
RTRAFFAM98AQ8NCA5727
RTRAFPOLR2AP24928620
RTRAFZBTB8OSQ8IWT0580
RTRAFTAF15Q92804495
RTRAFGSK3BP49841481
RTRAFSMU1Q2TAY7476
RTRAFTXNDC16Q9P2K2455
RTRAFILF2Q12905449
RTRAFLSM12Q3MHD2444

IntAct

200 interactions, top by confidence:

ABTypeScore
FAM98ARTRAFpsi-mi:“MI:0915”(physical association)0.810
RTRAFFAM98Apsi-mi:“MI:0915”(physical association)0.810
RTRAFRTCBpsi-mi:“MI:0915”(physical association)0.750
RTCBRTRAFpsi-mi:“MI:0915”(physical association)0.750
RTRAFRTRAFpsi-mi:“MI:0915”(physical association)0.730
RTRAFRTRAFpsi-mi:“MI:0407”(direct interaction)0.730
RTRAFDDX1psi-mi:“MI:0915”(physical association)0.720
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
CFTRESYT2psi-mi:“MI:0914”(association)0.710
DDX1FAM98Bpsi-mi:“MI:0915”(physical association)0.670
CFTRHAX1psi-mi:“MI:0914”(association)0.610
RTRAFPApsi-mi:“MI:0915”(physical association)0.580
PARTRAFpsi-mi:“MI:0915”(physical association)0.580
RTRAFPApsi-mi:“MI:0915”(physical association)0.570
PARTRAFpsi-mi:“MI:0915”(physical association)0.570
NINRTRAFpsi-mi:“MI:0915”(physical association)0.560
RTRAFNINpsi-mi:“MI:0915”(physical association)0.560

BioGRID (306): C14orf166 (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), C14orf166 (Two-hybrid), C14orf166 (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), C14orf166 (Affinity Capture-MS), ACTR3B (Co-fractionation), AHNAK (Co-fractionation), C14orf166 (Co-fractionation), C14orf166 (Co-fractionation), C14orf166 (Co-fractionation), C14orf166 (Co-fractionation), C14orf166 (Co-fractionation)

ESM2 similar proteins: A6H7C9, A7S7F2, A8WVM4, A9UL78, A9UNU6, G5EDM7, G5EG51, H2QII6, O14715, O44740, O54825, O60071, P30641, P31376, P38333, P49792, P51406, Q03280, Q0IHJ3, Q10573, Q13895, Q18508, Q20932, Q21341, Q291E4, Q54IS0, Q5E9N0, Q5R8I2, Q63ZS0, Q6BER5, Q6DFE2, Q6FRS1, Q6FS52, Q7ZUH1, Q80WL2, Q8MYL1, Q8RWS4, Q95Y84, Q96LK0, Q99666

Diamond homologs: Q5R8I2, Q63ZS0, Q7ZUH1, Q9CQE8, Q9Y224

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO termPartnersFoldFDR
stress granule assembly521.8×6e-04
intrinsic apoptotic signaling pathway615.6×6e-04
mRNA stabilization513.3×5e-03
G1/S transition of mitotic cell cycle811.6×1e-04
positive regulation of fibroblast proliferation510.7×9e-03
positive regulation of miRNA transcription510.5×9e-03
negative regulation of translation79.9×1e-03
cytoplasmic translation68.1×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

16 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance0
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1381 predictions. Top by Δscore:

VariantEffectΔscore
14:51989697:AAAGG:Adonor_loss1.0000
14:51989698:AAGG:Adonor_loss1.0000
14:51989700:GGT:Gdonor_loss1.0000
14:51989701:GTGAG:Gdonor_loss1.0000
14:51991310:A:AGacceptor_gain1.0000
14:51991315:A:AGacceptor_gain1.0000
14:51991315:AGAT:Aacceptor_gain1.0000
14:51991316:G:GCacceptor_gain1.0000
14:51991316:GA:Gacceptor_gain1.0000
14:51991316:GAT:Gacceptor_gain1.0000
14:51991316:GATG:Gacceptor_gain1.0000
14:51991316:GATGA:Gacceptor_gain1.0000
14:51991442:G:GGdonor_gain1.0000
14:51991442:GTAAT:Gdonor_loss1.0000
14:51991443:T:Gdonor_loss1.0000
14:51991454:G:GTdonor_gain1.0000
14:51993720:C:Gacceptor_gain1.0000
14:51993721:A:AGacceptor_gain1.0000
14:51993721:A:Gacceptor_loss1.0000
14:51993722:G:GAacceptor_gain1.0000
14:51993722:GT:Gacceptor_gain1.0000
14:51993722:GTAT:Gacceptor_gain1.0000
14:51993722:GTATC:Gacceptor_gain1.0000
14:51993819:AATGG:Adonor_loss1.0000
14:51993820:ATGG:Adonor_loss1.0000
14:51993821:TGGTA:Tdonor_loss1.0000
14:51993823:G:GAdonor_loss1.0000
14:51993824:TA:Tdonor_loss1.0000
14:51998488:TTATA:Tacceptor_loss1.0000
14:51998490:ATAGC:Aacceptor_loss1.0000

AlphaMissense

1622 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
14:51991346:T:AW31R1.000
14:51991346:T:CW31R1.000
14:51991350:T:CL32P1.000
14:51991355:G:CD34H1.000
14:51991356:A:TD34V1.000
14:51991359:A:CQ35P1.000
14:51991368:G:CR38T1.000
14:51991368:G:TR38M1.000
14:51991369:G:CR38S1.000
14:51991369:G:TR38S1.000
14:51991389:G:CR45T1.000
14:51991389:G:TR45I1.000
14:51991390:A:CR45S1.000
14:51991390:A:TR45S1.000
14:51991401:G:CR49T1.000
14:51991402:A:CR49S1.000
14:51991402:A:TR49S1.000
14:51991421:T:AW56R1.000
14:51991421:T:CW56R1.000
14:51993799:T:AV88D1.000
14:51999746:G:CA138P1.000
14:52004383:C:AA201D1.000
14:52004392:T:CL204P1.000
14:52004416:T:CL212P1.000
14:52004419:G:CR213T1.000
14:52004419:G:TR213I1.000
14:52004420:A:CR213S1.000
14:52004420:A:TR213S1.000
14:52004425:T:CL215P1.000
14:52004429:G:CQ216H1.000

dbSNP variants (sampled 300 via entrez): RS1000041219 (14:51990811 CTTA>C), RS1000056572 (14:51992827 T>C), RS1000173336 (14:52005175 T>G), RS1000213083 (14:52004845 T>C), RS1000237193 (14:51996727 C>A), RS1000329013 (14:52004587 A>G), RS1000550596 (14:52008134 A>G), RS1000581797 (14:52007941 C>G,T), RS1000639427 (14:51998860 G>A), RS1000824771 (14:52003012 A>C), RS1000886833 (14:52010492 A>C), RS1000974984 (14:51987800 C>G), RS1001020704 (14:51992568 A>G), RS1001071194 (14:51994249 A>G), RS1001131920 (14:51994029 C>G)

Disease associations

OMIM: gene MIM:610858 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

StudyTraitp-value
GCST004412_11Craniofacial microsomia1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067445 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects cotreatment, decreases methylation, decreases expression3
Cyclosporineincreases expression2
2,4,6-tribromophenoldecreases expression1
arseniteaffects binding, increases reaction1
tetrabromobisphenol Adecreases expression1
chloropicrinincreases expression1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
Resveratrolincreases expression, affects cotreatment1
Fulvestrantaffects cotreatment, decreases methylation1
Air Pollutantsincreases abundance, decreases expression1
Aminoglutethimidedecreases expression1
Arsenicdecreases expression1
Benzo(a)pyreneaffects methylation1
Catechinaffects cotreatment, decreases expression1
Cisplatinincreases expression1
Doxorubicindecreases expression1
Enzyme Inhibitorsdecreases activity, increases O-linked glycosylation1
Ivermectindecreases expression1
Leadaffects expression1
Plant Extractsincreases expression, affects cotreatment1
Tretinoindecreases expression1
Josamycinaffects response to substance1
Aflatoxin B1decreases methylation1
Sodium Seleniteincreases expression1
Antirheumatic Agentsincreases expression1
Copper Sulfatedecreases expression1
Particulate Matterdecreases expression, increases abundance1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5652876BindingBinding affinity to human C14orf166 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): craniofacial microsomia