NEMF

Summary

NEMF (nuclear export mediator factor, HGNC:10663) is a protein-coding gene on chromosome 14q21.3, encoding Ribosome quality control complex subunit NEMF (O60524). Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degradation.

This gene encodes a component of the ribosome quality control complex. The encoded protein facilitates the recognition and ubiquitination of stalled 60S subunits by the ubiquitin ligase listerin. A similar protein in fly functions as a tumor suppressor.

Source: NCBI Gene 9147 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with speech delay and axonal peripheral neuropathy (Strong, ClinGen)
• Clinical variants (ClinVar): 207 total — 18 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_004713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10663
Approved symbol	NEMF
Name	nuclear export mediator factor
Location	14q21.3
Locus type	gene with protein product
Status	Approved
Aliases	NY-CO-1, FLJ10051, RQC2
Ensembl gene	ENSG00000165525
Ensembl biotype	protein_coding
OMIM	608378
Entrez	9147

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 protein_coding, 7 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000298310, ENST00000553696, ENST00000554162, ENST00000554275, ENST00000554626, ENST00000555411, ENST00000555863, ENST00000555970, ENST00000556074, ENST00000556672, ENST00000556691, ENST00000556882, ENST00000556925, ENST00000557193, ENST00000557380, ENST00000925603, ENST00000925604, ENST00000943722

RefSeq mRNA: 2 — MANE Select: NM_004713 NM_001301732, NM_004713

CCDS: CCDS9694

Canonical transcript exons

ENST00000298310 — 33 exons

Exon	Start	End
ENSE00001093773	49833423	49833496
ENSE00001093777	49840718	49840866
ENSE00001253649	49852695	49852788
ENSE00001856904	49782083	49784713
ENSE00003480292	49806021	49806133
ENSE00003486587	49800420	49800696
ENSE00003495315	49828291	49828354
ENSE00003506256	49825867	49825955
ENSE00003507742	49838139	49838206
ENSE00003521106	49799475	49799524
ENSE00003524801	49803237	49803294
ENSE00003526825	49831299	49831361
ENSE00003533487	49851563	49851665
ENSE00003541812	49832207	49832277
ENSE00003564424	49813988	49814050
ENSE00003565601	49789496	49789573
ENSE00003570633	49851807	49851875
ENSE00003578675	49785092	49785135
ENSE00003584326	49829054	49829262
ENSE00003585979	49786718	49786750
ENSE00003588979	49832051	49832126
ENSE00003595118	49789146	49789343
ENSE00003605864	49784925	49785004
ENSE00003610570	49802453	49802573
ENSE00003636060	49795791	49795944
ENSE00003642908	49828616	49828807
ENSE00003656082	49829349	49829426
ENSE00003664080	49846140	49846265
ENSE00003667583	49785220	49785320
ENSE00003668971	49814754	49814857
ENSE00003684879	49802669	49802727
ENSE00003692010	49799636	49799678
ENSE00003789256	49834363	49834449

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2994 / max 1004.7530, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143091	22.5146	1796
143092	1.7848	864

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.26	gold quality
tendon	UBERON:0000043	97.26	gold quality
medial globus pallidus	UBERON:0002477	97.24	gold quality
sperm	CL:0000019	97.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.14	gold quality
globus pallidus	UBERON:0001875	97.11	gold quality
pylorus	UBERON:0001166	96.88	gold quality
corpus callosum	UBERON:0002336	96.75	gold quality
lateral globus pallidus	UBERON:0002476	96.75	gold quality
colonic epithelium	UBERON:0000397	96.70	gold quality
sural nerve	UBERON:0015488	96.68	gold quality
inferior vagus X ganglion	UBERON:0005363	96.52	gold quality
tendon of biceps brachii	UBERON:0008188	96.32	gold quality
oocyte	CL:0000023	96.29	gold quality
endothelial cell	CL:0000115	96.20	gold quality
visceral pleura	UBERON:0002401	96.17	gold quality
subthalamic nucleus	UBERON:0001906	96.13	gold quality
substantia nigra pars compacta	UBERON:0001965	96.12	gold quality
cardia of stomach	UBERON:0001162	95.99	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.79	gold quality
renal medulla	UBERON:0000362	95.56	gold quality
ventral tegmental area	UBERON:0002691	95.51	gold quality
cervix squamous epithelium	UBERON:0006922	95.46	gold quality
superior vestibular nucleus	UBERON:0007227	95.43	gold quality
adrenal tissue	UBERON:0018303	95.39	gold quality
tonsil	UBERON:0002372	95.33	gold quality
primary visual cortex	UBERON:0002436	95.21	gold quality
amniotic fluid	UBERON:0000173	95.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-150-5P	99.99	66.69	1976
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-33A-3P	99.70	70.27	3362

Literature-anchored findings (GeneRIF, showing 2)

• Results show that Listerin specificity for nascent chain-60S complexes depends on nuclear export mediator factor. (PMID:25578875)
• Biallelic loss-of-function variants in NEMF cause central nervous system impairment and axonal polyneuropathy. (PMID:33048237)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000102859
mus_musculus	Nemf	ENSMUSG00000020982
rattus_norvegicus	AABR07064719.2	ENSRNOG00000056128
drosophila_melanogaster	Clbn	FBGN0259152
caenorhabditis_elegans		WBGENE00022350

Protein

Protein identifiers

Ribosome quality control complex subunit NEMF — O60524 (reviewed: O60524)

Alternative names: Antigen NY-CO-1, Nuclear export mediator factor, Serologically defined colon cancer antigen 1

All UniProt accessions (4): O60524, G3V4D9, G3V547, G3V5V3

UniProt curated annotations — full annotation on UniProt →

Function. Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degradation. Thereby, frees 60S subunit ribosomes from the stalled translation complex and prevents the accumulation of nascent polypeptide chains that are potentially toxic for the cell. Within the RQC complex, NEMF specifically binds stalled 60S ribosomal subunits by recognizing an exposed, nascent chain-conjugated tRNA moiety and promotes the recruitment of LTN1 to stalled 60S subunits. Following binding to stalled 60S ribosomal subunits, NEMF mediates CAT tailing by recruiting alanine-charged tRNA to the A-site and directing the elongation of stalled nascent chains independently of mRNA or 40S subunits, leading to non-templated C-terminal alanine extensions (CAT tails). Mainly recruits alanine-charged tRNAs, but can also other amino acid-charged tRNAs. CAT tailing is required to promote ubiquitination of stalled nascent chains by different E3 ubiquitin-protein ligases. In the canonical RQC pathway (RQC-L), CAT tailing facilitates LTN1-dependent ubiquitination by exposing lysine residues that would otherwise remain buried in the ribosomal exit tunnel. In the alternative RQC pathway (RQC-C) CAT tailing creates an C-degron mainly composed of alanine that is recognized by the CRL2(KLHDC10) and RCHY1/PIRH2 E3 ligases, leading to ubiquitination and degradation of stalled nascent chains. NEMF may also indirectly play a role in nuclear export.

Subunit / interactions. Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit. The complex probably also contains VCP/p97 and its ubiquitin-binding cofactors. Interacts (via its N-terminus) with XPO1.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Expressed in brain, heart, liver, lung, spleen, and skeletal muscle. Also expressed at lower levels in stomach and testis.

Disease relevance. Intellectual developmental disorder with speech delay and axonal peripheral neuropathy (IDDSAPN) [MIM:619099] An autosomal recessive disorder characterized by mild global developmental delay, mild to moderate intellectual disability, motor impairment, unsteady or ataxic gait, and severe speech delay apparent in the first years of life. Signs of a peripheral axonal neuropathy, including progressive distal muscle weakness and atrophy of the lower limbs, foot and hand deformities, and dysarthria, are observed in most patients. Some patients may have autistic features or attention deficit-hyperactivity disorder. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NEMF family.

Isoforms (5)

UniProt ID	Names	Canonical?
O60524-1	1	yes
O60524-2	2
O60524-3	3
O60524-4	4
O60524-5	5

RefSeq proteins (2): NP_001288661, NP_004704* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008532	NFACT_RNA-bd	Domain
IPR021846	NFACT-C	Domain
IPR051608	RQC_Subunit_NEMF	Family

Pfam: PF05670, PF05833, PF11923

UniProt features (41 total): compositionally biased region 9, sequence conflict 7, modified residue 6, splice variant 5, sequence variant 5, region of interest 3, coiled-coil region 3, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9GY4	ELECTRON MICROSCOPY	3
3J92	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60524-F1	69.96	0.23

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 (6): 7, 417, 747, 748, 763, 831

Mutagenesis-validated functional residues (2):

Position	Phenotype
96–97	abolished ability to mediate cat tailing.
96	abolished ability to mediate cat tailing.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide

MSigDB gene sets: 188 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT, MODULE_379, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_TRANSLATIONAL_ELONGATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_NUCLEAR_EXPORT

GO Biological Process (8): nuclear export (GO:0051168), protein-containing complex assembly (GO:0065003), rescue of stalled cytosolic ribosome (GO:0072344), CAT tailing (GO:0140708), ribosome-associated ubiquitin-dependent protein catabolic process (GO:1990116), tRNA 3’-terminal CCA addition (GO:0001680), tRNA 3’-end processing (GO:0042780), ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627)

GO Molecular Function (3): tRNA binding (GO:0000049), ribosomal large subunit binding (GO:0043023), alpha-aminoacyl-tRNA binding (GO:1904678)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), cytosolic ribosome (GO:0022626), RQC complex (GO:1990112), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Ribosome-associated quality control	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasmic translational elongation	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
RNA binding	2
cellular anatomical structure	2
nucleocytoplasmic transport	1
intercellular transport	1
cellular component assembly	1
protein-containing complex organization	1
ribosome disassembly	1
rescue of stalled cytosolic ribosome	1
ribosome-associated ubiquitin-dependent protein catabolic process	1
CCA tRNA nucleotidyltransferase activity	1
tRNA 3’-end processing	1
CC tRNA cytidylyltransferase activity	1
ATP:3’-cytidine-cytidine-tRNA adenylyltransferase activity	1
tRNA processing	1
RNA 3’-end processing	1
ribosome binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytosol	1
ribosome	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEMF	LTN1	O94822	968
NEMF	TCF25	Q9BQ70	864
NEMF	ANKZF1	Q9H8Y5	796
NEMF	ZNF598	Q86UK7	795
NEMF	VCP	P55072	792
NEMF	HBS1L	Q9Y450	767
NEMF	ABCE1	P61221	731
NEMF	AARS1	P49588	674
NEMF	PELO	Q9BRX2	667
NEMF	TARS1	P26639	643
NEMF	ASCC3	Q8N3C0	640
NEMF	ASCC2	Q9H1I8	625
NEMF	UFD1	Q92890	624
NEMF	GTPBP2	Q9BX10	620
NEMF	NPLOC4	Q8TAT6	612

IntAct

33 interactions, top by confidence:

A	B	Type	Score
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
NEMF	HADHB	psi-mi:“MI:0915”(physical association)	0.400
NEMF	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
GRB7	RIOK3	psi-mi:“MI:0914”(association)	0.350
rep	NEMF	psi-mi:“MI:0914”(association)	0.350
EZR	NEMF	psi-mi:“MI:0914”(association)	0.350
RPL11	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPL19	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPL5	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SPANXN2	ZNF320	psi-mi:“MI:0914”(association)	0.350
AKR7L	KIF2A	psi-mi:“MI:0914”(association)	0.350
CFAP141	WDR46	psi-mi:“MI:0914”(association)	0.350
GNL2	POLR1G	psi-mi:“MI:0914”(association)	0.350
PSENEN	KIF1C	psi-mi:“MI:0914”(association)	0.350
SPCS1	DHX16	psi-mi:“MI:0914”(association)	0.350
TCEAL7	DHX16	psi-mi:“MI:0914”(association)	0.350
CERS6	NEMF	psi-mi:“MI:0914”(association)	0.350
KLK12	NEMF	psi-mi:“MI:0914”(association)	0.350
FOSL2	IFT56	psi-mi:“MI:0914”(association)	0.350
LUC7L2	SAP18	psi-mi:“MI:0914”(association)	0.350
UCHL5	KIF2A	psi-mi:“MI:0914”(association)	0.350
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
RPS11	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A2VE39, A9X1A0, B0KWC1, B1MTG7, B2KI64, B4UT09, D2HRF1, D4A1X2, F1R777, F1RA39, O00418, O00763, O02810, O08561, O08796, O60524, O82486, O94851, P70531, Q05AW9, Q2HVD6, Q49GP3, Q4R8L2, Q5R981, Q5U2Z5, Q5XK84, Q5ZJD3, Q5ZJT0, Q5ZKK7, Q69ZX6, Q6EU10, Q6GN16, Q6NY89, Q7ZVV1, Q80TJ7, Q86U44, Q86X55, Q8BKC8, Q8C3P7, Q8CCP0

Diamond homologs: O60524, Q12532, Q8CCP0, Q9USN8, Q9VBX1, Q59020, O34693

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MECP2	“up-regulates activity”	NEMF	binding
NEMF	“form complex”	“RQC complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	6	20.6×	2e-05
Viral mRNA Translation	6	20.6×	2e-05
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	20.4×	2e-05
Selenocysteine synthesis	6	19.5×	2e-05
Eukaryotic Translation Termination	6	19.5×	2e-05
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	19.1×	2e-05
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	19.1×	2e-05
SRP-dependent cotranslational protein targeting to membrane	7	18.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	6	26.5×	3e-05
translation	6	14.7×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	9
Uncertain significance	121
Likely benign	27
Benign	6

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1319076	NM_004713.6(NEMF):c.2068del (p.Leu690fs)	Pathogenic
2075049	NM_004713.6(NEMF):c.2484dup (p.Leu829fs)	Pathogenic
2136466	NM_004713.6(NEMF):c.1410T>G (p.Tyr470Ter)	Pathogenic
2153920	NM_004713.6(NEMF):c.1334_1337del (p.Gln445fs)	Pathogenic
2231009	NM_004713.6(NEMF):c.517del (p.Glu172_Ile173insTer)	Pathogenic
2410827	NM_004713.6(NEMF):c.2020dup (p.Arg674fs)	Pathogenic
3063692	NM_004713.6(NEMF):c.1066C>T (p.Gln356Ter)	Pathogenic
3572987	NM_004713.6(NEMF):c.2338dup (p.Thr780fs)	Pathogenic
3778420	NM_004713.6(NEMF):c.1923_1924del (p.Asn642fs)	Pathogenic
973826	NM_004713.6(NEMF):c.2011C>T (p.Arg671Ter)	Pathogenic
973827	NM_004713.6(NEMF):c.1A>T (p.Met1Leu)	Pathogenic
973828	NM_004713.6(NEMF):c.2768del (p.Lys923fs)	Pathogenic
986400	NM_004713.6(NEMF):c.2608C>T (p.Arg870Ter)	Pathogenic
986401	NM_004713.6(NEMF):c.2014A>T (p.Lys672Ter)	Pathogenic
986402	NM_004713.6(NEMF):c.2871_2875dup (p.Asp959delinsValTer)	Pathogenic
986403	NM_004713.6(NEMF):c.2618del (p.Lys873fs)	Pathogenic
986405	NM_004713.6(NEMF):c.1234_1235insC (p.Asn412fs)	Pathogenic
992634	NM_004713.6(NEMF):c.1235_1236insC (p.Pro413fs)	Pathogenic
1334763	NM_004713.6(NEMF):c.2096-2A>G	Likely pathogenic
1687703	NM_004713.6(NEMF):c.438del (p.Lys146fs)	Likely pathogenic
2574740	NM_004713.6(NEMF):c.235C>T (p.Arg79Ter)	Likely pathogenic
2630635	NM_004713.6(NEMF):c.1336_1340del (p.Gln445_Lys446insTer)	Likely pathogenic
3342433	NM_004713.6(NEMF):c.2587dup (p.Ala863fs)	Likely pathogenic
3900673	NM_004713.6(NEMF):c.979C>T (p.Arg327Ter)	Likely pathogenic
931494	NM_004713.6(NEMF):c.807-2A>C	Likely pathogenic
973823	NM_004713.6(NEMF):c.2777C>T (p.Pro926Leu)	Likely pathogenic
993000	NM_004713.6(NEMF):c.574+1G>T	Likely pathogenic

SpliceAI

5590 predictions. Top by Δscore:

Variant	Effect	Δscore
14:49782365:TGCA:T	acceptor_loss	1.0000
14:49782367:CAG:C	acceptor_loss	1.0000
14:49782368:A:AG	acceptor_gain	1.0000
14:49782368:A:AT	acceptor_loss	1.0000
14:49782368:AG:A	acceptor_gain	1.0000
14:49782369:G:A	acceptor_loss	1.0000
14:49782369:G:GA	acceptor_gain	1.0000
14:49782369:GG:G	acceptor_gain	1.0000
14:49782369:GGT:G	acceptor_gain	1.0000
14:49782369:GGTT:G	acceptor_gain	1.0000
14:49782369:GGTTA:G	acceptor_gain	1.0000
14:49782453:GAGCT:G	donor_gain	1.0000
14:49782454:AGCT:A	donor_gain	1.0000
14:49782455:GCT:G	donor_gain	1.0000
14:49782455:GCTG:G	donor_gain	1.0000
14:49782456:CT:C	donor_gain	1.0000
14:49782457:TGTA:T	donor_loss	1.0000
14:49782458:G:GG	donor_gain	1.0000
14:49782458:GTA:G	donor_loss	1.0000
14:49782459:TAAG:T	donor_loss	1.0000
14:49782462:G:GG	donor_gain	1.0000
14:49782540:A:AG	acceptor_gain	1.0000
14:49782541:G:GG	acceptor_gain	1.0000
14:49785000:TGCAG:T	acceptor_gain	1.0000
14:49785001:GCAG:G	acceptor_gain	1.0000
14:49785002:CAG:C	acceptor_gain	1.0000
14:49785002:CAGC:C	acceptor_gain	1.0000
14:49785003:AG:A	acceptor_gain	1.0000
14:49785004:GCTG:G	acceptor_loss	1.0000
14:49785005:C:CC	acceptor_gain	1.0000

AlphaMissense

7165 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:49785112:C:T	G1018E	1.000
14:49785121:A:G	L1015P	1.000
14:49789521:C:G	R891P	1.000
14:49803247:G:C	F635L	1.000
14:49803247:G:T	F635L	1.000
14:49803248:A:G	F635S	1.000
14:49803249:A:G	F635L	1.000
14:49803254:C:T	G633E	1.000
14:49803263:A:C	L630W	1.000
14:49803263:A:G	L630S	1.000
14:49803286:T:A	K622N	1.000
14:49803286:T:G	K622N	1.000
14:49803287:T:A	K622I	1.000
14:49803288:T:C	K622E	1.000
14:49803293:A:T	V620E	1.000
14:49806066:C:A	W604C	1.000
14:49806066:C:G	W604C	1.000
14:49806068:A:G	W604R	1.000
14:49806068:A:T	W604R	1.000
14:49806070:G:T	A603D	1.000
14:49814010:G:C	S574R	1.000
14:49814010:G:T	S574R	1.000
14:49814012:T:G	S574R	1.000
14:49814804:C:T	G544E	1.000
14:49814830:G:C	S535R	1.000
14:49814830:G:T	S535R	1.000
14:49814832:T:G	S535R	1.000
14:49825943:C:G	A501P	1.000
14:49825946:A:G	S500P	1.000
14:49828299:C:G	A494P	1.000

dbSNP variants (sampled 300 via entrez): RS1000166763 (14:49806409 C>A,G,T), RS1000198373 (14:49791030 G>C), RS1000226567 (14:49797564 G>C), RS1000348701 (14:49791144 G>A,T), RS1000405126 (14:49834865 A>G), RS1000408471 (14:49809114 C>T), RS1000419891 (14:49785161 C>A,G,T), RS1000423687 (14:49791315 G>A,C), RS1000443025 (14:49820776 C>T), RS1000449559 (14:49796521 T>A), RS1000453110 (14:49839011 G>A), RS1000511496 (14:49813195 T>C,G), RS1000531676 (14:49819746 GGAGA>G,GGA), RS1000584951 (14:49813464 G>A), RS1000586730 (14:49839229 C>T)

Disease associations

OMIM: gene MIM:608378 | disease phenotypes: MIM:619099

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with speech delay and axonal peripheral neuropathy	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
intellectual developmental disorder with speech delay and axonal peripheral neuropathy	Strong	AR

Mondo (3): intellectual developmental disorder with speech delay and axonal peripheral neuropathy (MONDO:0030849), prostate cancer (MONDO:0008315), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Familial prostate cancer (Orphanet:1331), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001337	Tremor
HP:0002098	Respiratory distress
HP:0002751	Kyphoscoliosis
HP:0003477	Peripheral axonal neuropathy
HP:0003593	Infantile onset
HP:0003693	Distal amyotrophy
HP:0011463	Childhood onset

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression, increases methylation	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases reaction, increases expression	1
sodium arsenate	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Cadmium	decreases expression	1
Caffeine	increases phosphorylation	1
Estradiol	increases reaction, affects binding	1
Methyl Methanesulfonate	increases expression	1
Phenolsulfonphthalein	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Metribolone	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer