MYRF

Summary

MYRF (myelin regulatory factor, HGNC:1181) is a protein-coding gene on chromosome 11q12.2, encoding Myelin regulatory factor (Q9Y2G1). Constitutes a precursor of the transcription factor.

This gene encodes a transcription factor that is required for central nervous system myelination and may regulate oligodendrocyte differentiation. It is thought to act by increasing the expression of genes that effect myelin production but may also directly promote myelin gene expression. Loss of a similar gene in mouse models results in severe demyelination. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 745 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiac-urogenital syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 142 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 464 total — 38 pathogenic, 40 likely-pathogenic (top 7% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 10 regions constrained (≈12% of expected missense variation)
• GTEx eGene: eQTL in 21 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 44
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.21 (highly constrained)
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_001127392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1181
Approved symbol	MYRF
Name	myelin regulatory factor
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	Ndt80, pqn-47, MRF
Ensembl gene	ENSG00000124920
Ensembl biotype	protein_coding
OMIM	608329
Entrez	745

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 22 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000278836

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 2, TSL 5: 1

ENST00000278836, ENST00000265460, ENST00000389602, ENST00000536352, ENST00000537318, ENST00000537766, ENST00000539361, ENST00000546247, ENST00000675319, ENST00000675345, ENST00000675792, ENST00000856798, ENST00000856799, ENST00000856800, ENST00000856801, ENST00000856802, ENST00000856803, ENST00000856804, ENST00000856805, ENST00000856806, ENST00000856807, ENST00000856808, ENST00000856809, ENST00000856810, ENST00000856811, ENST00000856812, ENST00000856813, ENST00000918478, ENST00000918479, ENST00001141511

RefSeq mRNA: 2 — MANE Select: NM_001127392 NM_001127392, NM_013279

CCDS: CCDS31579, CCDS44622

Canonical transcript exons

ENST00000278836 — 27 exons

Exon	Start	End
ENSE00000851667	61770246	61770525
ENSE00000851668	61769260	61769321
ENSE00000851669	61765958	61766221
ENSE00000916469	61777734	61777845
ENSE00000916471	61777264	61777464
ENSE00000916474	61776787	61776877
ENSE00000916486	61771829	61771952
ENSE00000916488	61771500	61771750
ENSE00001140120	61776322	61776432
ENSE00001196708	61752636	61752790
ENSE00001228603	61783498	61783600
ENSE00001324593	61765625	61765712
ENSE00001357447	61776056	61776132
ENSE00001506342	61773967	61774162
ENSE00001726169	61784280	61784385
ENSE00001757101	61785800	61785874
ENSE00001803334	61783851	61783925
ENSE00001806276	61779263	61779423
ENSE00002268635	61786063	61788518
ENSE00002319261	61778380	61778489
ENSE00003462587	61780712	61780792
ENSE00003502350	61780222	61780290
ENSE00003506782	61781138	61781329
ENSE00003526766	61779498	61779570
ENSE00003529284	61781573	61781824
ENSE00003568414	61779842	61779930
ENSE00003642612	61780960	61781045

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4766 / max 1290.5938, expressed in 1002 samples.

Highest expression (Bgee): middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion, spinal cord, inferior olivary complex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MYRF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	5.9e-54	-0.58	11:61747198:G:C
Liver	eqtl	4.0e-45	-0.85	11:61756894:A:C
Whole Blood	eqtl	6.8e-30	-0.35	11:61756647:G:A
Cells Cultured fibroblasts	eqtl	4.0e-21	-0.25	11:61756647:G:A
Adipose Subcutaneous	eqtl	6.5e-13	-0.24	11:61756894:A:C
Cells EBV-transformed lymphocytes	eqtl	5.8e-10	-0.28	11:61756647:G:A
Spleen	eqtl	5.7e-09	-0.58	11:61753974:C:A
Testis	eqtl	3.1e-07	-0.24	11:61729279:T:C
Nerve Tibial	eqtl	5.4e-07	-0.18	11:61758258:G:A
Colon Transverse	eqtl	1.1e-06	-0.24	11:61757035:T:C
Esophagus Muscularis	eqtl	1.9e-06	-0.18	11:61753974:C:A
Artery Tibial	eqtl	3.4e-06	-0.20	11:61756647:G:A
Pancreas	eqtl	5.1e-04	-0.16	11:61758258:G:A
Esophagus Gastroesophageal Junction	eqtl	2.0e-03	+0.44	11:61717684:C:T
Thyroid	eqtl	2.3e-03	-0.18	11:61757502:G:A
Breast Mammary Tissue	eqtl	5.4e-03	-0.20	11:61753196:T:C
Brain Cerebellum	eqtl	7.0e-03	+0.55	11:60787365:G:A
Prostate	eqtl	1.2e-02	-0.87	11:61562732:G:A
Heart Left Ventricle	eqtl	1.6e-02	-0.94	11:61612389:G:A
Ovary	eqtl	2.6e-02	-1.79	11:62272305:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
114597	22.8323	1000
114600	0.3329	152
114599	0.1994	54
114601	0.1016	54
114598	0.0103	4

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle frontal gyrus	UBERON:0002702	99.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.81	gold quality
inferior vagus X ganglion	UBERON:0005363	98.71	gold quality
spinal cord	UBERON:0002240	98.64	gold quality
inferior olivary complex	UBERON:0002127	98.45	gold quality
medulla oblongata	UBERON:0001896	97.31	gold quality
subthalamic nucleus	UBERON:0001906	97.23	gold quality
ventral tegmental area	UBERON:0002691	96.86	gold quality
lateral globus pallidus	UBERON:0002476	96.80	gold quality
superior vestibular nucleus	UBERON:0007227	96.25	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.20	gold quality
midbrain	UBERON:0001891	96.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.17	gold quality
pigmented layer of retina	UBERON:0001782	96.14	gold quality
substantia nigra	UBERON:0002038	96.09	gold quality
corpus callosum	UBERON:0002336	95.79	gold quality
putamen	UBERON:0001874	95.78	gold quality
pylorus	UBERON:0001166	95.44	gold quality
gall bladder	UBERON:0002110	95.24	gold quality
globus pallidus	UBERON:0001875	94.82	gold quality
cranial nerve II	UBERON:0000941	94.76	gold quality
Ammon’s horn	UBERON:0001954	94.64	gold quality
CA1 field of hippocampus	UBERON:0003881	94.50	gold quality
amygdala	UBERON:0001876	94.27	gold quality
medial globus pallidus	UBERON:0002477	94.20	gold quality
right lung	UBERON:0002167	94.16	gold quality
body of pancreas	UBERON:0001150	94.04	gold quality
caudate nucleus	UBERON:0001873	94.01	gold quality
substantia nigra pars compacta	UBERON:0001965	93.64	gold quality
pons	UBERON:0000988	93.58	gold quality
left uterine tube	UBERON:0001303	93.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.11	gold quality
cardia of stomach	UBERON:0001162	92.95	gold quality
postcentral gyrus	UBERON:0002581	92.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.71	gold quality
parietal lobe	UBERON:0001872	92.64	gold quality
germinal epithelium of ovary	UBERON:0001304	92.63	gold quality
pancreatic ductal cell	CL:0002079	92.45	gold quality
hypothalamus	UBERON:0001898	92.28	gold quality
body of stomach	UBERON:0001161	92.13	gold quality
upper lobe of left lung	UBERON:0008952	91.92	gold quality
stomach	UBERON:0000945	91.85	gold quality
pancreas	UBERON:0001264	91.85	gold quality
right frontal lobe	UBERON:0002810	91.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.69	gold quality
nucleus accumbens	UBERON:0001882	91.28	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.26	gold quality
temporal lobe	UBERON:0001871	91.18	gold quality
upper lobe of lung	UBERON:0008948	90.87	gold quality
prefrontal cortex	UBERON:0000451	90.47	gold quality
telencephalon	UBERON:0001893	90.45	gold quality
islet of Langerhans	UBERON:0000006	89.93	gold quality
left ovary	UBERON:0002119	89.69	gold quality
frontal cortex	UBERON:0001870	89.65	gold quality
frontal lobe	UBERON:0016525	89.65	gold quality
cerebral cortex	UBERON:0000956	88.68	gold quality
lower esophagus mucosa	UBERON:0035834	88.61	gold quality
fundus of stomach	UBERON:0001160	88.57	gold quality
body of uterus	UBERON:0009853	88.56	gold quality
occipital lobe	UBERON:0002021	88.35	gold quality
neocortex	UBERON:0001950	88.32	gold quality
right ovary	UBERON:0002118	87.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.66	gold quality
forebrain	UBERON:0001890	87.61	gold quality
central nervous system	UBERON:0001017	87.39	gold quality
ovary	UBERON:0000992	87.13	gold quality
endothelial cell	CL:0000115	87.11	silver quality
right lobe of liver	UBERON:0001114	87.10	gold quality
brain	UBERON:0000955	87.02	gold quality
superior frontal gyrus	UBERON:0002661	86.96	gold quality
entorhinal cortex	UBERON:0002728	86.92	gold quality
cingulate cortex	UBERON:0003027	86.92	gold quality
anterior cingulate cortex	UBERON:0009835	86.82	gold quality
epithelial cell of pancreas	CL:0000083	86.55	silver quality
lung	UBERON:0002048	86.43	gold quality
primary visual cortex	UBERON:0002436	86.21	gold quality
orbitofrontal cortex	UBERON:0004167	86.19	gold quality
duodenum	UBERON:0002114	86.16	gold quality
sural nerve	UBERON:0015488	85.98	gold quality
metanephros cortex	UBERON:0010533	85.60	gold quality
frontal pole	UBERON:0002795	85.17	gold quality
paraflocculus	UBERON:0005351	84.37	gold quality
parietal pleura	UBERON:0002400	83.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.85	gold quality
olfactory bulb	UBERON:0002264	83.80	gold quality
small intestine	UBERON:0002108	83.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.18	gold quality
type B pancreatic cell	CL:0000169	82.84	gold quality
peritoneum	UBERON:0002358	82.13	gold quality
omental fat pad	UBERON:0010414	82.13	gold quality
jejunal mucosa	UBERON:0000399	81.01	gold quality
right coronary artery	UBERON:0001625	80.74	gold quality
liver	UBERON:0002107	80.43	gold quality
ileal mucosa	UBERON:0000331	80.38	gold quality
adult organism	UBERON:0007023	80.35	gold quality
granulocyte	CL:0000094	80.31	gold quality
cerebellar hemisphere	UBERON:0002245	80.25	gold quality
cerebellar cortex	UBERON:0002129	80.23	gold quality
myometrium	UBERON:0001296	80.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6108	yes	122.62
E-GEOD-84465	yes	12.51
E-ANND-3	yes	4.33

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	217.4
Nucleus accumbens	tissue	107.0
Medulla oblongata	tissue	99.5
Spinal cord	tissue	98.7
Substantia nigra	tissue	93.9
Midbrain	tissue	92.5
Locus coeruleus	tissue	78.3
Thalamus	tissue	72.7
Ventral forebrain	tissue	72.1
Superior colliculi	tissue	70.5
Putamen	tissue	68.0
Pons	tissue	67.4
Hippocampus	tissue	65.3
Periaqueductal gray	tissue	59.9
Hypothalamus	tissue	58.5
Stomach 1	tissue	47.8
Hippocampal formation	tissue	46.0
Septum	tissue	44.3
Postcentral gyrus	tissue	34.9
Cerebral cortex	tissue	33.8
Retrosplenial cortex	tissue	33.8
Amygdala	tissue	31.3
Somatosensory cortex	tissue	30.1
Insular cortex	tissue	29.1
Motor cortex	tissue	28.7
Occipital cortex	tissue	27.5
Caudate putamen	tissue	26.7
Prefrontal cortex	tissue	24.6
Retrosplenial and cingulate cortex	tissue	23.2
Basal ganglia	tissue	22.1
Temporal cortex	tissue	19.5
Pancreas	tissue	18.3
Entorhinal cortex	tissue	17.7
Gallbladder	tissue	16.2
Olfactory bulb	tissue	15.7
Lung	tissue	11.6
Choroid plexus	tissue	10.8
Duodenum	tissue	10.8
Small intestine	tissue	10.1
Frontal cortex	tissue	9.1
Cerebellum	tissue	8.4
Fallopian tube	tissue	4.6
Endometrium 1	tissue	3.8
Ovary	tissue	2.5
Liver	tissue	2.4
Colon	tissue	2.2
Cervix	tissue	1.8
Smooth muscle	tissue	1.8
Kidney	tissue	1.8
Testis	tissue	1.6
Placenta	tissue	1.1
Appendix	tissue	1.1
Rectum	tissue	1.0
Esophagus	tissue	0.8
Heart muscle	tissue	0.4
Retina	tissue	0.3
Seminal vesicle	tissue	0.3
Urinary bladder	tissue	0.3
Vagina	tissue	0.2
Adipose tissue	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (374.4), Temporal white matter (352.1), Corpus callosum, splenium (white matter) (303.3), Corpus callosum, genu (white matter) (270.3), Nucleus raphe obscurus (251.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets:

Target	Regulation
ABCB1
ADAM2
CDR2
COL5A2
EIF3K
FGF2
MIR499A
MYF6
MYH7B
MYOG
SMARCA4
STAB1

miRNA regulators (miRDB)

Targeting MYRF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 142 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.215, missense Z 3.56 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000278836 splits into 10 regions with different missense tolerance; 3 are missense-constrained (≈12% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:61,752,745–61,771,645	368 / 403.9	0.91	no
11:61,771,646–61,774,025	87 / 129.2	0.67	no
11:61,774,026–61,774,065	1 / 16.7	0.06	yes (p 1.2e-04)
11:61,774,066–61,776,067	36 / 47.5	0.76	no
11:61,776,068–61,776,108	1 / 18.1	0.06	yes (p 5.7e-05)
11:61,776,109–61,776,353	23 / 26.6	0.86	no
11:61,776,354–61,777,402	48 / 148.2	0.32	yes (p 1.9e-16)
11:61,777,403–61,779,501	123 / 209.1	0.59	no
11:61,779,502–61,783,536	323 / 383.1	0.84	no
11:61,783,537–61,786,140	94 / 164.6	0.57	no

Literature-anchored findings (GeneRIF, showing 21)

• A Bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound transcription factor, the myelin regulatory factor MYRF. (PMID:23966832)
• molecular mechanisms underlying the homo-trimerization of Myrf N-terminal fragments and the homo-trimeric DNA binding of Myrf N-terminal fragments (PMID:28160598)
• The relative scarcity of oligodendrocyte lineage cells expressing MYRF in demyelinated MS lesions demonstrates, for the first time, that chronic lesions lack oligodendrocytes that express this necessary transcription factor for remyelination and supports the notion that a failure to fully differentiate underlies remyelination failure. (PMID:28631093)
• Functional defects of MYRF are likely to be causally associated with encephalopathy with extensive myelin vacuolization (PMID:29265453)
• Heterozygous variants in MYRF should be considered in patients with variants of Scimitar syndrome and urogenital anomalies. (PMID:29446546)
• We identified four unrelated individuals with congenital diaphragmatic hernia with damaging de novo variants in MYRF (P = 5.3x10(-8)), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. (PMID:30532227)
• The results suggest that MYRF is a novel causative gene of 46,XY and 46,XX disorders of sex development and MYRF is a transcription factor regulating coelomic epithelium and/or coelomic epithelium derived cells proliferation and migration, which is essential for development of multiple organs. (PMID:30985895)
• Identified a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), which produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. (PMID:31048900)
• results underline the importance of including SLC18A3 sequencing in the differential diagnostics of fetuses with arthrogryposis, FADS, or LMPS of unknown etiology (PMID:31069960)
• These evidence all support that truncation mutations in the C-terminal region of MYRF are responsible for autosomal dominant high hyperopia in these families. (PMID:31172260)
• This is the first trio-based whole-genome sequencing (WGS), study for nanophthalmos, revealing the potential role of de novo mutations (DNMs) in MYRF and rare inherited genetic variants in PRSS56 and MFRP. (PMID:31266062)
• C-terminal variants in MYRF, which are expected to escape nonsense-mediated decay, represent a rare cause of autosomal dominant nanophthalmos with or without dextrocardia or congenital diaphragmatic hernia. (PMID:31700225)
• Functional mechanism and pathogenic potential of MYRF ICA domain mutations implicated in birth defects. (PMID:31964908)
• The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort. (PMID:32052405)
• Pancreatic Cancer Cells Require the Transcription Factor MYRF to Maintain ER Homeostasis. (PMID:32997974)
• Common Myelin Regulatory Factor Gene Variants Predisposing to Excellence in Sports. (PMID:33670313)
• Functional mechanisms of MYRF DNA-binding domain mutations implicated in birth defects. (PMID:33798553)
• MYRF: A Mysterious Membrane-Bound Transcription Factor Involved in Myelin Development and Human Diseases. (PMID:33864620)
• Evaluation of MYRF as a candidate gene for primary angle closure glaucoma. (PMID:35136345)
• Truncation mutations in MYRF underlie primary angle closure glaucoma. (PMID:36129575)
• Two sisters with cardiac-urogenital syndrome secondary to pathogenic splicing variant in the MYRF gene with unaffected parents: A case of gonadal mosaicism? (PMID:36695166)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	myrf	ENSDARG00000078676
mus_musculus	Myrf	ENSMUSG00000036098
rattus_norvegicus	Myrf	ENSRNOG00000028274
drosophila_melanogaster	CG3328	FBGN0034985
caenorhabditis_elegans		WBGENE00004134
caenorhabditis_elegans		WBGENE00008999

Paralogs (1): MYRFL (ENSG00000166268)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2684944) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
tremors	1
abnormal myelination	1
abnormal oligodendrocyte morphology	1
abnormal spinal cord morphology	1
retina degeneration	1
abnormal optic nerve morphology	1
ataxia	1
abnormal embryo size	1
abnormal embryo turning	1
seizures	1
abnormal retina inner nuclear layer morphology	1
embryonic growth retardation	1
abnormal rod electrophysiology	1
abnormal cone electrophysiology	1
abnormal retina pigmentation	1
retina pigment epithelium atrophy	1
decreased retina cone cell number	1
thin retina outer nuclear layer	1
short photoreceptor inner segment	1
short photoreceptor outer segment	1
postnatal lethality, complete penetrance	1
preweaning lethality, complete penetrance	1
increased cornea thickness	1
decreased total retina thickness	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	F1N4M2	82.4%	Diamond
Xenopus laevis	Q66IV1	58.1%	Diamond
Dictyostelium discoideum	Q1ZXA9	42.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MYRF-AS1	ncRNA	26070
MIR611	ncRNA	693196
TMEM258	protein-coding	746
DAGLA	protein-coding	747
SYT7	protein-coding	9066
MIR1908	ncRNA	100302263
FEN1	protein-coding	2237
FADS1	protein-coding	3992
FADS2	protein-coding	9415

Protein

Protein identifiers

Myelin regulatory factor — Q9Y2G1 (reviewed: Q9Y2G1)

Alternative names: Myelin gene regulatory factor

All UniProt accessions (4): A0A6Q8PFL7, A0A6Q8PFY9, A0A6Q8PHM1, Q9Y2G1

UniProt curated annotations — full annotation on UniProt →

Function. Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes. Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage. Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5’-CTGGYAC-3’ in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype.

Subunit / interactions. Homotrimer. Interacts (via C-terminal region) with TMEM98; the interaction inhibits MYRF self-cleavage.

Subcellular location. Endoplasmic reticulum membrane Nucleus. Cytoplasm Endoplasmic reticulum membrane.

Tissue specificity. Expressed in lung, brainstem, uterus and, to a lesser extent, in basal ganglion and liver. Weakly expressed in cerebellum. High expression detected in the retinal pigment epithelium, choroid, and optic nerve.

Post-translational modifications. Glycosylated. Follows autocatalytic cleavage via the peptidase S74 domain. Autoprocessing is apparently constitutive and is essential for transcriptional activity. Autocatalytic cleavage is inhibited by interaction with TMEM98.

Disease relevance. Encephalitis/encephalopathy, mild, with reversible myelin vacuolization (MMERV) [MIM:618113] An autosomal dominant disease characterized by episodes of acute encephalitis associated with impaired consciousness, delirious behavior, seizures, and reversible splenial lesions observed on diffusion magnetic resonance imaging. Most patients completely recover and there are no neurologic sequelae. MMERV occurs in children and is frequently associated with a trigger, such as a febrile illness. The disease may be caused by variants affecting the gene represented in this entry. Cardiac-urogenital syndrome (CUGS) [MIM:618280] An autosomal dominant syndrome characterized by partial anomalous pulmonary venous return, tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. The disease is caused by variants affecting the gene represented in this entry. Nanophthalmos 1 (NNO1) [MIM:600165] A form of nanophthalmos, a disorder of eye development characterized by extreme hyperopia and small functional eyes. The cornea and lens are normal in size and shape. Hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. NNO1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The nuclear localization signals mediate translocation to the nucleus. The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components.

Similarity. Belongs to the MRF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2G1-1	1	yes
Q9Y2G1-2	2

RefSeq proteins (2): NP_001120864, NP_037411 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR024061	NDT80_DNA-bd_dom	Domain
IPR025719	MYRF_C2	Domain
IPR026932	MYRF_ICA	Domain
IPR030392	S74_ICA	Domain
IPR037141	NDT80_DNA-bd_dom_sf	Homologous_superfamily
IPR051577	MRF-like	Family

Pfam: PF05224, PF13884, PF13887, PF13888

UniProt features (74 total): strand 18, mutagenesis site 10, sequence variant 9, region of interest 5, compositionally biased region 5, glycosylation site 4, chain 3, splice variant 3, sequence conflict 3, short sequence motif 2, topological domain 2, turn 2, helix 2, coiled-coil region 1, site 1, modified residue 1, transmembrane region 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
5YHU	Crystal structure of the DNA-binding domain of human myelin-gene regulatory factor	X-RAY DIFFRACTION	1.85
5ZHU	Crystal structure of the DNA-binding domain of human myelin-gene regulatory factor	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2G1-F1	61.76	0.29

Human Protein Atlas

Protein class: Predicted membrane proteins, Plasma proteins, Transcription factors, Immunoglobulin fold, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
586–587	cleavage; by autolysis

Post-translational modifications (1)

Type	Positions
N6-acetyllysine	123

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	919, 1043, 1065, 1129

Mutagenesis-validated functional residues (10)

Position	Phenotype
454	decreased affinity for dna.
478	decreased affinity for dna.
530	decreased affinity for dna.
587	prevents autocatalytic cleavage and generation of myelin regulatory factor, n-terminal part.
588	reduces autocatalytic cleavage and generation of myelin regulatory factor, n-terminal part.
592	prevents autocatalytic cleavage and generation of myelin regulatory factor, n-terminal part.
608	does not affect autocatalytic cleavage.
635	reduces autocatalytic cleavage and generation of myelin regulatory factor, n-terminal part.
688	does not affect autocatalytic cleavage.
699	prevents autocatalytic cleavage and generation of myelin regulatory factor, n-terminal part.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 341 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, RNGTGGGC_UNKNOWN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_COCAINE, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, TGCACTT_MIR519C_MIR519B_MIR519A, CROONQUIST_NRAS_SIGNALING_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_GLIAL_CELL_DEVELOPMENT, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, GOBP_NEUROGENESIS, CREBP1_Q2

GO Biological Process (14): DNA-templated transcription (GO:0006351), oligodendrocyte development (GO:0014003), protein autoprocessing (GO:0016540), central nervous system myelination (GO:0022010), positive regulation of myelination (GO:0031643), central nervous system myelin maintenance (GO:0032286), response to immobilization stress (GO:0035902), response to cocaine (GO:0042220), positive regulation of DNA-templated transcription (GO:0045893), oligodendrocyte differentiation (GO:0048709), positive regulation of oligodendrocyte differentiation (GO:0048714), regulation of DNA-templated transcription (GO:0006355), proteolysis (GO:0006508), cell differentiation (GO:0030154)

GO Molecular Function (7): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), peptidase activity (GO:0008233), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), hydrolase activity (GO:0016787), identical protein binding (GO:0042802)

GO Cellular Component (5): nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

47 GO namespaces:

Category	Terms
cellular anatomical structure	3
oligodendrocyte differentiation	2
myelination	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
gene expression	1
RNA biosynthetic process	1
glial cell development	1
protein processing	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
regulation of myelination	1
positive regulation of nervous system process	1
positive regulation of cellular process	1
central nervous system myelination	1
myelin maintenance	1
response to stress	1
response to alkaloid	1
response to oxygen-containing compound	1
positive regulation of RNA biosynthetic process	1
central nervous system development	1
glial cell differentiation	1
positive regulation of glial cell differentiation	1
regulation of oligodendrocyte differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein metabolic process	1
cellular developmental process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
DNA binding	1
nucleic acid binding	1
catalytic activity	1
protein binding	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

showing 15 of 796 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYRF	BEST1	O76090	812
MYRF	FEN1	P39748	773
MYRF	SOX10	P56693	749
MYRF	MBP	P02686	730
MYRF	HDAC3	O15379	683
MYRF	OLIG2	Q13516	676
MYRF	OLIG1	Q8TAK6	675
MYRF	PLP1	P04400	666
MYRF	SPO11	Q9Y5K1	656
MYRF	PDGFRA	P16234	590
MYRF	TMEM98	Q9Y2Y6	590
MYRF	NKX2-2	O95096	587
MYRF	MOBP	Q13875	583
MYRF	MOG	Q16653	580
MYRF	RFFL	Q8WZ73	571

IntAct

BioGRID (26 interactions; top human partners by supporting records): AP1G1 (Co-fractionation), AP1S1 (Co-fractionation), AP1S2 (Co-fractionation), ATG16L1 (Proximity Label-MS), GPRC5B (Affinity Capture-MS), GRAMD3 (Affinity Capture-MS), KCNE3 (Affinity Capture-MS), NRAS (Proximity Label-MS), PCDHB3 (Affinity Capture-MS), PTPRF (Co-fractionation), TOP3B (Affinity Capture-RNA), TRIM71 (Affinity Capture-RNA)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MAP2K1	“down-regulates activity”	MYRF	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for MYRF: 464 ClinVar records (78 pathogenic / likely pathogenic); 142 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	40
Uncertain significance	189
Likely benign	123
Benign	28

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 78 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
620313	NM_001127392.3(MYRF):c.2817G>A (p.Trp939Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1527967	NM_001127392.3(MYRF):c.1702del (p.Asp568fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
929443	NM_001127392.3(MYRF):c.2572+1G>A	Pathogenic	criteria provided, single submitter	2
996608	NM_001127392.3(MYRF):c.1435C>G (p.Leu479Val)	Pathogenic	criteria provided, single submitter	2
2441925	NM_001127392.3(MYRF):c.1543C>T (p.Gln515Ter)	Pathogenic	criteria provided, single submitter	2
3777343	NM_001127392.3(MYRF):c.1116-3C>G	Pathogenic	criteria provided, single submitter	2
985076	NM_001127392.3(MYRF):c.2358_2359del (p.Tyr787fs)	Pathogenic	criteria provided, single submitter	1
985959	NM_001127392.3(MYRF):c.2041del (p.Ala681fs)	Pathogenic	criteria provided, single submitter	1
1013323	NM_001127392.3(MYRF):c.1705G>T (p.Glu569Ter)	Pathogenic	criteria provided, single submitter	1
1176284	NM_001127392.3(MYRF):c.350del (p.Gly117fs)	Pathogenic	criteria provided, single submitter	1
1180013	NM_001127392.3(MYRF):c.1072C>T (p.Gln358Ter)	Pathogenic	criteria provided, single submitter	1
1698932	NM_001127392.3(MYRF):c.648C>A (p.Tyr216Ter)	Pathogenic	criteria provided, single submitter	1
2307379	NM_001127392.3(MYRF):c.1207C>T (p.Gln403Ter)	Pathogenic	criteria provided, single submitter	1
2582895	NM_001127392.3(MYRF):c.871C>T (p.Arg291Ter)	Pathogenic	criteria provided, single submitter	1
2584483	NM_001127392.3(MYRF):c.2956C>T (p.Arg986Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore MYRF’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 2,746):

Position(s)	Effect	Δscore	Sites
11:61752791–61752792	donor_loss	1.0000	4
11:61765623–61765624	acceptor_loss	1.0000	5
11:61765713–61765714	donor_loss	1.0000	3
11:61770522	donor_gain	1.0000
11:61771827–61771828	acceptor_loss	1.0000	6
11:61774163	donor_loss	1.0000
11:61776133–61776134	donor_loss	1.0000	4
11:61776320–61776321	acceptor_loss	1.0000	5
11:61776433–61776434	donor_loss	1.0000	4
11:61777451	donor_gain	1.0000

AlphaMissense

2,752 missense substitutions predicted likely pathogenic (of 7,511 scored), across 596 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M489	9	0.995	1.000
M676	9	0.948	0.998
M776	9	0.917	0.999
M610	9	0.889	0.998
M580	9	0.833	0.985
N400	8	1.000	1.000
H401	8	1.000	1.000
H480	8	1.000	1.000
D382	8	0.999	1.000
F402	8	0.999	1.000
F481	8	0.999	1.000
N488	8	0.999	1.000
F385	8	0.998	1.000
F502	8	0.998	1.000
N533	8	0.998	1.000
F537	8	0.998	1.000
D498	8	0.995	1.000
N496	8	0.994	1.000
D391	8	0.993	1.000
N487	8	0.993	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Stomach Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	unfavorable	5.43e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000148
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	0.000286

Disease associations

OMIM: gene MIM:608329 | disease phenotypes: MIM:618280, MIM:618113, MIM:600165, MIM:142340, MIM:236750

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
cardiac-urogenital syndrome	Strong	Autosomal dominant	4
hyperopia	Strong	Autosomal dominant
encephalitis/encephalopathy, mild, with reversible myelin vacuolization	Limited	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
cardiac-urogenital syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Anophthalmia or microphthalmia	green
DDG2P	green
Differences in sex development	green
Fetal anomalies	green
Paediatric disorders	green
Structural eye disease	green

Mondo (10): cardiac-urogenital syndrome (MONDO:0032653), disorder of sexual differentiation (MONDO:0002145), neurodevelopmental disorder (MONDO:0700092), encephalitis/encephalopathy, mild, with reversible myelin vacuolization (MONDO:0020853), nanophthalmos 1 (MONDO:0010836), congenital diaphragmatic hernia (MONDO:0005711), urogenital tract malformation (MONDO:0019356), non-immune hydrops fetalis (MONDO:0009369), dextrocardia (MONDO:0015661), hyperopia (MONDO:0004891)

Orphanet (7): Cardiac-urogenital syndrome (Orphanet:647811), Difference of sex development (Orphanet:90771), Nanophthalmos (Orphanet:35612), Congenital diaphragmatic hernia (Orphanet:2140), Urogenital tract malformation (Orphanet:83001), Non-immune hydrops fetalis (Orphanet:363999), Dextrocardia (Orphanet:1666)

HPO phenotypes

44 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000105	Enlarged kidney
HP:0000151	Aplasia of the uterus
HP:0000431	Wide nasal bridge
HP:0000776	Congenital diaphragmatic hernia
HP:0000808	Penoscrotal hypospadias
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001643	Patent ductus arteriosus
HP:0001649	Tachycardia
HP:0001651	Dextrocardia
HP:0001698	Pericardial effusion
HP:0001747	Accessory spleen
HP:0002089	Pulmonary hypoplasia
HP:0002566	Intestinal malrotation
HP:0002779	Tracheomalacia
HP:0002780	Bronchomalacia
HP:0003010	Prolonged bleeding time
HP:0003621	Juvenile onset
HP:0004383	Hypoplastic left ventricle
HP:0004691	2-3 toe syndactyly
HP:0006846	Acute encephalopathy
HP:0007633	Bilateral microphthalmos
HP:0010479	Patent urachus
HP:0010773	Partial anomalous pulmonary venous return
HP:0011463	Childhood onset
HP:0011599	Mesocardia
HP:0011611	Interrupted aortic arch
HP:0011626	Scimitar anomaly
HP:0012741	Unilateral cryptorchidism
HP:0030732	Dysplastic tricuspid valve
HP:0031134	Cor triatriatum sinister
HP:0031298	Coronary sinus enlargement
HP:0034198	Second trimester onset
HP:0200128	Biventricular hypertrophy
HP:0410259	Hepatopulmonary fusion

GWAS associations

showing 30 of 142 associations:

Study	Trait	p-value
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002712_4	Red blood cell fatty acid levels	3e-305
GCST002446_1	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4e-274
GCST002444_5	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5e-168
GCST001179_1	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	1e-151
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7e-147
GCST002448_6	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	4e-140
GCST012020_387	Serum metabolite levels	4e-98
GCST002712_2	Red blood cell fatty acid levels	8e-90
GCST006613_72	Triglycerides	2e-86
GCST012020_386	Serum metabolite levels	4e-83
GCST002450_8	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2e-72
GCST001180_4	Plasma omega-3 polyunsaturated fatty acid levels (alphalinolenic acid)	1e-63
GCST001178_6	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	6e-58
GCST012020_381	Serum metabolite levels	1e-47
GCST002712_9	Red blood cell fatty acid levels	6e-43
GCST009391_2117	Metabolite levels	2e-41
GCST005650_172	Serum metabolite ratios in chronic kidney disease	8e-36
GCST001834_7	Oleic acid (18:1n-9) levels	2e-32
GCST003818_6	Resting heart rate	2e-30
GCST012020_382	Serum metabolite levels	6e-29
GCST010083_16	Hemoglobin levels	1e-28
GCST012020_383	Serum metabolite levels	8e-26
GCST010002_191	Refractive error	2e-24
GCST005650_120	Serum metabolite ratios in chronic kidney disease	5e-24
GCST005650_180	Serum metabolite ratios in chronic kidney disease	7e-24
GCST006611_20	HDL cholesterol	2e-22
GCST005650_176	Serum metabolite ratios in chronic kidney disease	9e-22
GCST002446_7	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	3e-21
GCST004601_25	Red blood cell count	4e-21

EFO canonical traits (from GWAS)

31 canonical traits:

EFO ID	Trait name
EFO:0007760	eicosapentaenoic acid measurement
EFO:0006809	docosapentaenoic acid measurement
EFO:0007759	alpha-linolenic acid measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0005094	P wave duration
EFO:0006810	oleic acid measurement
EFO:0006808	arachidonic acid measurement
EFO:0006807	linoleic acid measurement
EFO:0006811	linolenic acid measurement
EFO:0006334	total iron binding capacity
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count
EFO:0007764	delta-5 desaturase measurement
EFO:0009131	response to polyunsaturated fatty acid supplementation
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0009594	irritability measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:1002011	adult onset asthma
EFO:0009963	bipolar I disorder
EFO:0004469	HOMA-B
EFO:0010382	phosphatidylcholine 36:4 measurement
EFO:0005059	acylcarnitine measurement
EFO:0010118	sphingomyelin measurement
EFO:0006944	systolic blood pressure change measurement
EFO:0010119	omega-3 polyunsaturated fatty acid measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D003914	Dextrocardia	C14.240.400.280; C14.280.400.280; C16.131.240.400.280; C16.131.810.250
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
D006956	Hyperopia	C11.744.479
D065886	Neurodevelopmental Disorders	F03.625
C563983	Nanophthalmos 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Benzo(a)pyrene	increases methylation, increases expression	2
Cisplatin	increases expression, affects response to substance, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Capecitabine	increases response to substance	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Lead	affects methylation	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
Antirheumatic Agents	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 425 trials:

NCT	Phase	Status	Title
NCT00347204	Phase 4	COMPLETED	Comparison of Acular LS Versus Nevanac for Pain Control in Eyes Undergoing PRK
NCT00455455	Phase 4	COMPLETED	Corneal and Conjunctival Sensitivity and Staining Study
NCT00937105	Phase 4	COMPLETED	Daily Wear Corneal Infiltrative Event Study
NCT01387360	Phase 4	COMPLETED	Presbyopic Supracor Treatment for Near Myopic/Hyperopic Pseudophakic Eyes
NCT01977807	Phase 4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser in Asian Eyes Using LASIK
NCT02071576	Phase 4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser Using LASIK
NCT02112968	Phase 4	UNKNOWN	A Prospective Safety and Effectiveness Study of a New High Repetition Rate Excimer Laser Using LASIK for the Correction of Ammetropia and Presbyopia
NCT03881670	Phase 4	COMPLETED	On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours
NCT04208750	Phase 4	COMPLETED	Clinical Investigation of the Vision-R800 Device.
NCT04283331	Phase 4	UNKNOWN	Anesthetic Impregnated Bandage Soft Contact Lens (BSCL) in Pain Management After Photorefractive Keratectomy (PRK)
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	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	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	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	Phase 4	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	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	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	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	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	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment