RNF220

Summary

RNF220 (ring finger protein 220, HGNC:25552) is a protein-coding gene on chromosome 1p34.1, encoding E3 ubiquitin-protein ligase RNF220 (Q5VTB9). E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of SIN3B.

Enables beta-catenin binding activity. Involved in positive regulation of canonical Wnt signaling pathway. Acts upstream of or within positive regulation of DNA-binding transcription factor activity and protein monoubiquitination. Located in nuclear lamina and nucleoplasm. Part of protein-containing complex. Implicated in hypomyelinating leukodystrophy 23.

Source: NCBI Gene 55182 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 94 total — 2 pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_018150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25552
Approved symbol	RNF220
Name	ring finger protein 220
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10597
Ensembl gene	ENSG00000187147
Ensembl biotype	protein_coding
OMIM	616136
Entrez	55182

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding_CDS_not_defined, 6 protein_coding, 1 nonsense_mediated_decay

ENST00000335497, ENST00000355387, ENST00000361799, ENST00000440132, ENST00000453863, ENST00000470498, ENST00000471494, ENST00000474064, ENST00000474394, ENST00000474956, ENST00000475378, ENST00000480686, ENST00000484745, ENST00000487332, ENST00000488865, ENST00000496262, ENST00000497469, ENST00000925767

RefSeq mRNA: 7 — MANE Select: NM_018150 NM_001319956, NM_001319957, NM_001376486, NM_001376487, NM_001376488, NM_001376489, NM_018150

CCDS: CCDS510

Canonical transcript exons

ENST00000361799 — 15 exons

Exon	Start	End
ENSE00001404391	44411981	44412722
ENSE00003460836	44632343	44632385
ENSE00003481790	44645410	44645488
ENSE00003489902	44636030	44636162
ENSE00003498402	44614165	44614297
ENSE00003520465	44635545	44635588
ENSE00003585864	44644698	44644794
ENSE00003622362	44622742	44622787
ENSE00003642856	44644995	44645081
ENSE00003664246	44645221	44645276
ENSE00003676639	44650704	44651723
ENSE00003735266	44626297	44626398
ENSE00003786279	44649661	44649769
ENSE00003786730	44649883	44649957
ENSE00003849155	44405255	44405530

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.0110 / max 880.0356, expressed in 1825 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2621	46.2675	1823
2603	8.7091	442
2601	1.1790	400
2602	0.3089	169
2610	0.1466	36
2609	0.0934	41
2607	0.0884	42
2604	0.0793	49
2605	0.0613	31
2611	0.0504	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.43	gold quality
prefrontal cortex	UBERON:0000451	98.20	gold quality
right frontal lobe	UBERON:0002810	98.04	gold quality
spinal cord	UBERON:0002240	97.72	gold quality
anterior cingulate cortex	UBERON:0009835	97.57	gold quality
cingulate cortex	UBERON:0003027	97.55	gold quality
corpus callosum	UBERON:0002336	97.43	gold quality
frontal cortex	UBERON:0001870	97.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.95	gold quality
neocortex	UBERON:0001950	96.91	gold quality
granulocyte	CL:0000094	96.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.86	gold quality
nucleus accumbens	UBERON:0001882	96.67	gold quality
cerebellar hemisphere	UBERON:0002245	96.66	gold quality
cerebellar cortex	UBERON:0002129	96.64	gold quality
amygdala	UBERON:0001876	96.57	gold quality
caudate nucleus	UBERON:0001873	96.56	gold quality
putamen	UBERON:0001874	96.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.34	gold quality
cortical plate	UBERON:0005343	96.15	gold quality
telencephalon	UBERON:0001893	96.06	gold quality
cerebral cortex	UBERON:0000956	96.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.93	gold quality
body of uterus	UBERON:0009853	95.92	gold quality
lower esophagus	UBERON:0013473	95.92	gold quality
hypothalamus	UBERON:0001898	95.91	gold quality
apex of heart	UBERON:0002098	95.84	gold quality
Ammon’s horn	UBERON:0001954	95.83	gold quality
forebrain	UBERON:0001890	95.82	gold quality
cerebellum	UBERON:0002037	95.78	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	3715.43
E-HCAD-35	yes	3412.84
E-HCAD-25	yes	3183.82
E-ANND-3	yes	9.45
E-MTAB-7381	no	54.79
E-MTAB-6142	no	45.71
E-CURD-112	no	3.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting RNF220, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4487	99.96	64.58	1252
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4676-3P	99.65	69.31	1733

Literature-anchored findings (GeneRIF, showing 8)

• RNF220 interacts with USP7, a ubiquitin-specific peptidase, which is required for RNF220 to stabilize beta-catenin. (PMID:25266658)
• This variant could promote the RNF220 protein degradation. (PMID:30500349)
• RNF220 promotes the proliferation of leukaemic cells and reduces the degradation of the Cyclin D1 protein through USP22. (PMID:32896826)
• Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness. (PMID:33964137)
• CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid leukemia. (PMID:34702297)
• Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis. (PMID:34753387)
• Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression. (PMID:35040952)
• Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma. (PMID:37537194)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf220a	ENSDARG00000060929
danio_rerio	rnf220b	ENSDARG00000075183
mus_musculus	Rnf220	ENSMUSG00000028677
rattus_norvegicus	Rnf220	ENSRNOG00000019236
drosophila_melanogaster	RNF220	FBGN0039013

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF220 — Q5VTB9 (reviewed: Q5VTB9)

Alternative names: RING finger protein 220, RING-type E3 ubiquitin transferase RNF220

All UniProt accessions (5): Q5VTB9, H0Y7B1, Q5TDE7, Q5TDE8, U3KPZ6

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of SIN3B. Independently of its E3 ligase activity, acts as a CTNNB1 stabilizer through USP7-mediated deubiquitination of CTNNB1 promoting Wnt signaling. Plays a critical role in the regulation of nuclear lamina.

Subunit / interactions. Interacts with SIN3B. Interacts with CTNNB1 (via Armadillo repeats 2-8). Interacts with USP7 (via MATH domain).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed. Abundant in brain and spinal cord, particularly in the cerebellum and cerebral cortex. In fetal tissues expressed in the cerebellum, spinal cord and cortex.

Post-translational modifications. Auto-ubiquitinated; leads to proteasomal degradation.

Disease relevance. Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy (HLD23) [MIM:619688] An autosomal recessive neurodegenerative disorder with systemic manifestations. Affected individuals show delayed motor development and ataxic gait in early childhood that progresses to spastic paraplegia with loss of ambulation in the first decades of life. Additional features include progressive sensorineural hearing loss, hepatic dysfunction, and dilated cardiomyopathy. Death occurs in the first or second decades. Brain imaging shows hypomyelination, diffuse white matter abnormalities, and thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VTB9-1	1	yes
Q5VTB9-3	2

RefSeq proteins (7): NP_001306885, NP_001306886, NP_001363415, NP_001363416, NP_001363417, NP_001363418, NP_060620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR031824	RNF220_mid	Domain
IPR040178	RNF220_RING	Domain
IPR052443	E3_ubiq-ligase_RNF220-like	Family

Pfam: PF13923, PF15926

UniProt features (13 total): sequence variant 2, sequence conflict 2, region of interest 2, splice variant 2, chain 1, zinc finger region 1, coiled-coil region 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTB9-F1	59.21	0.18

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 (2): 390, 277

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 298 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MYOGENIN_Q6, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, XU_GH1_AUTOCRINE_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GCANCTGNY_MYOD_Q6, MAZ_Q6, MODULE_317, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY

GO Biological Process (9): noradrenergic neuron development (GO:0003358), protein monoubiquitination (GO:0006513), protein ubiquitination (GO:0016567), dorsal/ventral neural tube patterning (GO:0021904), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), protein autoubiquitination (GO:0051865), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), regulation of transcription regulatory region DNA binding (GO:2000677)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), beta-catenin binding (GO:0008013), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), protein-containing complex (GO:0032991), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein ubiquitination	2
synapse	2
noradrenergic neuron differentiation	1
neuron development	1
protein modification by small protein conjugation	1
dorsal/ventral pattern formation	1
neural tube patterning	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
regulation of receptor internalization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1
transcription cis-regulatory region binding	1
regulation of DNA binding	1
ubiquitin-like protein transferase activity	1
protein binding	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
nuclear periphery	1
nuclear lumen	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF220	ZC4H2	Q9NQZ6	742
RNF220	TMEM53	Q6P2H8	597
RNF220	ERI3	O43414	530
RNF220	CCDC24	Q8N4L8	497
RNF220	CTNNB1	P35222	483
RNF220	SIN3B	O75182	456
RNF220	ASB13	Q8WXK3	433
RNF220	SH3RF1	Q7Z6J0	423
RNF220	SLC24A2	Q9UI40	418
RNF220	DBX2	Q6ZNG2	396
RNF220	NEDD4L	Q96PU5	390
RNF220	MAN1A2	O60476	389
RNF220	VRK1	Q99986	387
RNF220	CUL7	Q14999	387
RNF220	B4GALT2	O60909	386

IntAct

34 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
UBE2E3	RNF220	psi-mi:“MI:0915”(physical association)	0.660
WDR5B	TCP1	psi-mi:“MI:0914”(association)	0.530
RPL27A	MRPS9	psi-mi:“MI:0914”(association)	0.530
RNF220	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
RNF220	UBE2E1	psi-mi:“MI:0915”(physical association)	0.370
UBE2E2	RNF220	psi-mi:“MI:0915”(physical association)	0.370
RNF220	UBE2W	psi-mi:“MI:0915”(physical association)	0.370
C1qbp		psi-mi:“MI:0914”(association)	0.350
CLEC3A	ZNF593	psi-mi:“MI:0914”(association)	0.350
UBE2E3	RCBTB2	psi-mi:“MI:0914”(association)	0.350
ZC4H2	RNF220	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
RPL27A	ZNF320	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RPL37		psi-mi:“MI:0914”(association)	0.350
ZNF653	URB1	psi-mi:“MI:0914”(association)	0.350
DDX54	SYNCRIP	psi-mi:“MI:0914”(association)	0.350
CHCHD2	RECQL4	psi-mi:“MI:0914”(association)	0.350
NOM1	RPS9	psi-mi:“MI:0914”(association)	0.350
CHCHD2	ZNF593	psi-mi:“MI:0914”(association)	0.350
ZC4H2	VAMP3	psi-mi:“MI:0914”(association)	0.350
DDX54	CLPX	psi-mi:“MI:0914”(association)	0.350
TCEAL1		psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLU	RNF220	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (80): RNF220 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), USP7 (Affinity Capture-Western), RNF220 (Affinity Capture-Western), GSK3B (Affinity Capture-Western), GOPC (Two-hybrid), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-MS), RNF220 (Affinity Capture-RNA), RNF220 (Reconstituted Complex), RNF220 (Reconstituted Complex)

ESM2 similar proteins: A2AQ25, A6NFD8, B3F209, E9PSK7, O14503, O35185, O35779, O35780, O54972, O95644, P03966, P12755, P15407, P15408, P17544, P18444, P18625, P47930, P51145, Q01826, Q08DV5, Q13469, Q5EA15, Q5R9C9, Q5RAI7, Q5T5P2, Q5VTB9, Q60591, Q60611, Q63379, Q6GQB5, Q6ISB3, Q6PDX6, Q6QB00, Q7TS99, Q86YP4, Q8HXD5, Q8N228, Q8R0S1, Q8TEK3

Diamond homologs: Q08DV5, Q5VTB9, Q6PDX6, Q8HXD5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF220	ubiquitination
RNF220	“down-regulates quantity by destabilization”	SIN3B	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
Antigen processing: Ubiquitination & Proteasome degradation	6	10.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein monoubiquitination	5	49.1×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	64
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1333093	NM_018150.4(RNF220):c.1094G>A (p.Arg365Gln)	Pathogenic
1333094	NM_018150.4(RNF220):c.1088G>A (p.Arg363Gln)	Pathogenic

SpliceAI

5418 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44405516:G:GT	donor_gain	1.0000
1:44411043:A:G	donor_gain	1.0000
1:44412718:CAGAT:C	donor_gain	1.0000
1:44412719:AGAT:A	donor_gain	1.0000
1:44412720:GAT:G	donor_gain	1.0000
1:44412720:GATG:G	donor_gain	1.0000
1:44412721:AT:A	donor_gain	1.0000
1:44412722:TG:T	donor_loss	1.0000
1:44412723:G:GG	donor_gain	1.0000
1:44412723:G:T	donor_loss	1.0000
1:44412724:T:A	donor_loss	1.0000
1:44438959:C:G	donor_gain	1.0000
1:44614160:A:AG	acceptor_gain	1.0000
1:44614160:ACTAG:A	acceptor_gain	1.0000
1:44614161:C:G	acceptor_gain	1.0000
1:44614162:TAGGT:T	acceptor_loss	1.0000
1:44614163:AG:A	acceptor_gain	1.0000
1:44614163:AGGTA:A	acceptor_loss	1.0000
1:44614164:GG:G	acceptor_gain	1.0000
1:44614164:GGTAA:G	acceptor_gain	1.0000
1:44614293:TCGAG:T	donor_loss	1.0000
1:44614294:CGAGG:C	donor_loss	1.0000
1:44614296:AGGTA:A	donor_loss	1.0000
1:44614298:GTA:G	donor_loss	1.0000
1:44614299:T:G	donor_loss	1.0000
1:44626293:CCA:C	acceptor_loss	1.0000
1:44626294:CA:C	acceptor_loss	1.0000
1:44626295:A:AG	acceptor_gain	1.0000
1:44626296:G:GT	acceptor_gain	1.0000
1:44626296:GT:G	acceptor_gain	1.0000

AlphaMissense

3710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44412171:T:A	L25Q	1.000
1:44412171:T:C	L25P	1.000
1:44412177:T:A	V27D	1.000
1:44412180:T:C	L28P	1.000
1:44412503:T:C	F136L	1.000
1:44412504:T:C	F136S	1.000
1:44412505:T:A	F136L	1.000
1:44412505:T:G	F136L	1.000
1:44614209:T:A	C224S	1.000
1:44614209:T:C	C224R	1.000
1:44614210:G:A	C224Y	1.000
1:44614210:G:C	C224S	1.000
1:44614211:C:G	C224W	1.000
1:44614218:T:C	C227R	1.000
1:44614219:G:A	C227Y	1.000
1:44614220:C:G	C227W	1.000
1:44632346:T:C	F304L	1.000
1:44632347:T:C	F304S	1.000
1:44632347:T:G	F304C	1.000
1:44632348:T:A	F304L	1.000
1:44632348:T:G	F304L	1.000
1:44632350:T:C	L305P	1.000
1:44632353:G:C	R306P	1.000
1:44632359:G:C	R308P	1.000
1:44632361:G:C	A309P	1.000
1:44632364:A:G	N310D	1.000
1:44632367:C:G	R311G	1.000
1:44632368:G:C	R311P	1.000
1:44636108:T:A	W358R	1.000
1:44636108:T:C	W358R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001458 (1:44501302 G>T), RS1000003820 (1:44596051 G>A,T), RS1000005168 (1:44446706 A>C), RS1000015757 (1:44589569 A>G), RS1000017785 (1:44442979 C>A,T), RS1000028713 (1:44426456 G>A), RS1000059223 (1:44468180 A>C,G), RS1000077345 (1:44606876 T>C), RS1000080763 (1:44426248 G>T), RS1000095069 (1:44439644 A>G), RS1000112059 (1:44564365 C>G,T), RS1000131451 (1:44474375 C>A), RS1000158449 (1:44467105 C>T), RS1000168428 (1:44616942 C>T), RS1000173726 (1:44451846 C>G)

Disease associations

OMIM: gene MIM:616136 | disease phenotypes: MIM:619688

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy	Strong	Autosomal recessive

Mondo (1): leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy (MONDO:0030514)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001347	Hyperreflexia
HP:0001644	Dilated cardiomyopathy
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003429	CNS hypomyelination
HP:0003477	Peripheral axonal neuropathy
HP:0011463	Childhood onset
HP:0033725	Thin corpus callosum

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003818_46	Resting heart rate	5.000000e-21
GCST005787_11	Heart rate response to exercise	7.000000e-12
GCST005787_16	Heart rate response to exercise	5.000000e-09
GCST005788_12	Heart rate response to recovery post exercise	9.000000e-10
GCST005789_3	Resting heart rate	1.000000e-07
GCST005845_1	Heart rate increase in response to exercise	6.000000e-12
GCST005847_1	Heart rate response to recovery post exercise (20 sec)	5.000000e-09
GCST005848_9	Heart rate response to recovery post exercise (50 sec)	1.000000e-12
GCST005849_10	Heart rate response to recovery post exercise (40 sec)	8.000000e-12
GCST005850_1	Heart rate response to recovery post exercise (30 sec)	3.000000e-11
GCST006103_8	Interleukin-6 levels	1.000000e-06
GCST007692_8	Chronic obstructive pulmonary disease	6.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0004810	interleukin-6 measurement

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	increases methylation, affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
ICG 001	increases 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
Temozolomide	increases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Lead	decreases expression	1
Methapyrilene	decreases methylation	1
Selenium	increases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression, increases abundance	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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