MAL

Summary

MAL (mal, T cell differentiation protein (MAL blood group), HGNC:6817) is a protein-coding gene on chromosome 2q11.1, encoding Myelin and lymphocyte protein (P21145). May be involved in vesicular trafficking from the Golgi apparatus to the cell membrane.

The protein encoded by this gene is a highly hydrophobic integral membrane protein belonging to the MAL family of proteolipids. The protein has been localized to the endoplasmic reticulum of T-cells and is a candidate linker protein in T-cell signal transduction. In addition, this proteolipid is localized in compact myelin of cells in the nervous system and has been implicated in myelin biogenesis and/or function. The protein plays a role in the formation, stabilization and maintenance of glycosphingolipid-enriched membrane microdomains. Down-regulation of this gene has been associated with a variety of human epithelial malignancies. Alternative splicing produces four transcript variants which vary from each other by the presence or absence of alternatively spliced exons 2 and 3.

Source: NCBI Gene 4118 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, hypomyelinating, 28 (Moderate, GenCC)
• Clinical variants (ClinVar): 25 total — 1 pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_002371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6817
Approved symbol	MAL
Name	mal, T cell differentiation protein (MAL blood group)
Location	2q11.1
Locus type	gene with protein product
Status	Approved
Aliases	MVP17, VIP17
Ensembl gene	ENSG00000172005
Ensembl biotype	protein_coding
OMIM	188860
Entrez	4118

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000309988, ENST00000349807, ENST00000353004, ENST00000354078, ENST00000489399, ENST00000874490, ENST00000874491

RefSeq mRNA: 4 — MANE Select: NM_002371 NM_002371, NM_022438, NM_022439, NM_022440

CCDS: CCDS2006, CCDS2007, CCDS2008, CCDS2009

Canonical transcript exons

ENST00000309988 — 4 exons

Exon	Start	End
ENSE00001158036	95049581	95049706
ENSE00001158043	95047959	95048126
ENSE00001209724	95053381	95053992
ENSE00001428868	95025708	95025885

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 28.8666 / max 2256.2819, expressed in 484 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21400	25.7716	460
21398	2.2896	268
21399	0.8053	209

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.98	gold quality
pharyngeal mucosa	UBERON:0000355	99.95	gold quality
lower esophagus mucosa	UBERON:0035834	99.94	gold quality
buccal mucosa cell	CL:0002336	99.91	gold quality
tongue squamous epithelium	UBERON:0006919	99.88	gold quality
renal medulla	UBERON:0000362	99.85	gold quality
epithelium of esophagus	UBERON:0001976	99.75	gold quality
body of tongue	UBERON:0011876	99.75	gold quality
oral cavity	UBERON:0000167	99.72	gold quality
cervix squamous epithelium	UBERON:0006922	99.68	gold quality
squamous epithelium	UBERON:0006914	99.56	gold quality
esophagus mucosa	UBERON:0002469	99.41	gold quality
inferior vagus X ganglion	UBERON:0005363	99.38	gold quality
metanephros cortex	UBERON:0010533	99.37	gold quality
olfactory bulb	UBERON:0002264	99.32	gold quality
amniotic fluid	UBERON:0000173	99.27	gold quality
inferior olivary complex	UBERON:0002127	99.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.18	gold quality
tongue	UBERON:0001723	99.16	gold quality
spinal cord	UBERON:0002240	99.13	gold quality
tibial nerve	UBERON:0001323	99.10	gold quality
middle frontal gyrus	UBERON:0002702	98.94	gold quality
adult mammalian kidney	UBERON:0000082	98.93	gold quality
medulla oblongata	UBERON:0001896	98.84	gold quality
corpus callosum	UBERON:0002336	98.83	gold quality
lateral globus pallidus	UBERON:0002476	98.81	gold quality
subthalamic nucleus	UBERON:0001906	98.74	gold quality
trigeminal ganglion	UBERON:0001675	98.73	gold quality
ventral tegmental area	UBERON:0002691	98.72	gold quality
gingiva	UBERON:0001828	98.65	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	9575.78
E-CURD-79	yes	1716.22
E-CURD-84	yes	1260.30
E-GEOD-124472	yes	1039.09
E-HCAD-10	yes	941.03
E-GEOD-114530	yes	894.97
E-MTAB-8911	yes	326.19
E-HCAD-4	yes	79.86
E-CURD-122	yes	77.11
E-HCAD-11	yes	29.22
E-MTAB-8410	yes	22.59
E-GEOD-84465	yes	13.99
E-CURD-46	yes	9.80
E-CURD-55	no	370.53
E-CURD-120	no	353.42

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
MMP9	Unknown
MYL9	Unknown

Upstream regulators (CollecTRI, top): RBPJ, SMO

miRNA regulators (miRDB)

27 targeting MAL, 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-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-6861-5P	96.23	67.19	800

Literature-anchored findings (GeneRIF, showing 37)

• The mal gene which is switched-off in all esophageal squamous cell carcinoma samples can be considered as a tumor suppressor gene (PMID:15188492)
• Caveolin-1 and MAL are located on prostasomes secreted by prostate cancer cells (PMID:15466889)
• Quantitative analysis carried out using pixel intensity variance demonstrated that the MAL protein is capable of modifying the plasma membrane, thereby increasing its resistance to detergent-induced pore formation. (PMID:16785208)
• Loss of MAL expression is aasociated with precancerous lesions of the esophagus (PMID:17151798)
• Promoter hypermethylation of MAL, shown to be present in colorectal adenomas and carcinomas and only rarely in normal mucosa. (PMID:17408629)
• promoter hypermethylation of MAL was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa (PMID:18346269)
• MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker. (PMID:19002170)
• Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. (PMID:19208741)
• suggesting the MAL gene as a new metastasis-suppressor candidate for head and neck cancer (PMID:19445022)
• Data show that MAL transcript levels were higher in the resistant ovarian cell lines. (PMID:19642140)
• MAL is normally expressed in laryngeal epithelial cells and its expression changes at early stages of carcinoma development. (PMID:19670627)
• Data suggest that the epigenetic inactivation of MAL, as a candidate tumor suppressor gene, can contribute to human epithelial cell carcinoma and may be served as a biomarker in HNSCC. (PMID:21092172)
• the methylation marker panel CADM1-M18 and MAL-M1 may serve as an alternative molecular triage tool for hrHPV-positive women. (PMID:21190187)
• Data show that a combination of CADM1 and MAL methylation could represent a promising candidate triage tool for hrHPV-positive women. (PMID:21389098)
• Data show that MAL regulates membrane order and the distribution of microtubule and transport vesicle docking machinery at the IS and, by doing so, ensures correct protein sorting of Lck and LAT to the cSMAC. (PMID:21508261)
• Data indicate that DNA methylation status of multiple genes CADM1, MAL and hsa-miR-124-2 was analyzed in human papillomavirus (hrHPV)-positive cervical scrape. (PMID:23176198)
• MAL protein plays an important role during oral carcinogenesis, MAL gene expression was significantly decreased in oral squamous cell carcinoma compared with normal epithelium. (PMID:23224601)
• hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. (PMID:23381221)
• CADM1 and MAL methylation levels increased proportional to severity of the underlying lesion (PMID:23456988)
• MAL hypermethylation is associated with esophageal carcinoma progression. (PMID:24088706)
• The MAL gene repression related with lymph node metastasis and poor prognosis in gastric cancer, suggesting that the MAL may be a new candidate node metastasis-suppressor gene for gastric cancer. (PMID:24511665)
• DNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer (PMID:25281766)
• Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2+/CIN3+ detection when used as triage tool on cervical scrapes of HPV positive women. (PMID:25667975)
• Data suggest that expression of MAL in cells confers both ETX (Clostridium perfringens epsilon-toxin) binding and susceptibility to ETX-mediated cell death; cells expressing rat MAL are 100 times more sensitive to ETX than cells expressing human MAL. (PMID:25993478)
• MAL is a critical element of the machinery for exosome secretion and may constitute a target for modulating exosome secretion by human T cells. (PMID:26109641)
• CADM1/MAL methylation increases with severity of cervical intraepithelial neoplasia (PMID:26219541)
• The use of CADM1, MAL, and MIR124-2 as biomarkers for full molecular screening in HIV infected women who are also positive for human papillomavirus. (PMID:26473640)
• Hypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer. (PMID:26482433)
• This study revealed that Merkel cell polyomavirus -negative Merkel cell carcinomas significantly expressed higher CADM1 and lower MAL than Merkel cell polyomavirus -positive Merkel cell carcinomas (PMID:26772392)
• MAL and TMEM220 were specifically methylated and were down-regulated in human gastric cancer. (PMID:27329150)
• In high-grade serous ovarian carcinoma patients, MAL was overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival. (PMID:28545541)
• Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Epsilon toxin (Etx) from Clostridium perfringens and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes. (PMID:29987189)
• Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure. (PMID:32463157)
• Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein. (PMID:33345332)
• MAL protein suppresses the metastasis and invasion of GC cells by interfering with the phosphorylation of STAT3. (PMID:35093120)
• MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2. (PMID:38461243)
• MAL, a potential immunotherapy target, is associated with poor prognosis in cancer patients. (PMID:38678596)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	malb	ENSDARG00000030094
danio_rerio	mala.2	ENSDARG00000043442
danio_rerio	mala.1	ENSDARG00000070401
mus_musculus	Mal	ENSMUSG00000027375
rattus_norvegicus	Mal	ENSRNOG00000015445
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLP2 (ENSG00000102007), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), CMTM7 (ENSG00000153551), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), CMTM4 (ENSG00000183723), CKLF (ENSG00000217555)

Protein

Protein identifiers

Myelin and lymphocyte protein — P21145 (reviewed: P21145)

Alternative names: T-lymphocyte maturation-associated protein

All UniProt accessions (1): P21145

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in vesicular trafficking from the Golgi apparatus to the cell membrane. Plays a role in the maintenance of the myelin sheath, and in axon-glia and glia-glia interactions.

Subunit / interactions. Interacts with PLP1.

Subcellular location. Membrane. Cell membrane.

Post-translational modifications. Lipoprotein.

Disease relevance. Leukodystrophy, hypomyelinating, 28 (HLD28) [MIM:620978] A form of hypomyelinating leukodystrophy, a group of heterogeneous disorders characterized by persistent deficit of myelin observed on brain imaging. HLD28 is an autosomal recessive form characterized by developmental delay and nystagmus in infancy, followed by significant learning disabilities and progressive motor deterioration within the first decade. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MAL family.

Isoforms (4)

UniProt ID	Names	Canonical?
P21145-1	A	yes
P21145-2	B
P21145-3	C
P21145-4	D

RefSeq proteins (4): NP_002362, NP_071883, NP_071884, NP_071885 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR013295	MAL	Family
IPR050578	MARVEL-CKLF_proteins	Family

Pfam: PF01284

UniProt features (15 total): topological domain 5, transmembrane region 4, splice variant 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21145-F1	89.40	0.68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 286 (showing top): GOBP_APICAL_PROTEIN_LOCALIZATION, BENPORATH_ES_WITH_H3K27ME3, MODULE_169, BIOCARTA_MAL_PATHWAY, LU_IL4_SIGNALING, JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (10): membrane raft polarization (GO:0001766), protein localization to paranode region of axon (GO:0002175), apoptotic process (GO:0006915), central nervous system development (GO:0007417), central nervous system myelination (GO:0022010), cell differentiation (GO:0030154), myelination (GO:0042552), apical protein localization (GO:0045176), protein insertion into plasma membrane (GO:0098737), positive regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902043)

GO Molecular Function (4): lipid binding (GO:0008289), peptidase activator activity involved in apoptotic process (GO:0016505), structural constituent of myelin sheath (GO:0019911), protein binding (GO:0005515)

GO Cellular Component (8): endoplasmic reticulum (GO:0005783), membrane (GO:0016020), apical plasma membrane (GO:0016324), Schmidt-Lanterman incisure (GO:0043220), plasma membrane raft (GO:0044853), membrane raft (GO:0045121), hinge region between urothelial plaques of apical plasma membrane (GO:0120003), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane region	3
binding	2
cellular anatomical structure	2
membrane raft distribution	1
protein localization to axon	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nervous system development	1
system development	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
cellular developmental process	1
axon ensheathment	1
intracellular protein localization	1
protein insertion into membrane	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
positive regulation of extrinsic apoptotic signaling pathway	1
apoptotic process	1
peptidase activator activity	1
structural molecule activity	1
myelin sheath	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
apical part of cell	1
compact myelin	1
plasma membrane	1
membrane raft	1
membrane microdomain	1
apical plasma membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

637 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAL	INF2	Q27J81	712
MAL	OCLN	Q16625	647
MAL	NPHP1	O15259	642
MAL	PLLP	Q9Y342	612
MAL	SEPTIN6	Q14141	497
MAL	MAG	P20916	488
MAL	CD2	P06729	483
MAL	TLR1	Q15399	470
MAL	MBP	P02686	447
MAL	MYD88	P78397	438
MAL	SLC12A1	Q13621	435
MAL	ASPA	P45381	421
MAL	PMP22	Q01453	407
MAL	PLP1	P04400	398
MAL	CADM1	Q9BY67	398

IntAct

276 interactions, top by confidence:

A	B	Type	Score
MAL	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.780
MAL	EDA	psi-mi:“MI:0915”(physical association)	0.780
EDA	MAL	psi-mi:“MI:0915”(physical association)	0.780
KLRC1	MAL	psi-mi:“MI:0915”(physical association)	0.720
FIBCD1	MAL	psi-mi:“MI:0915”(physical association)	0.720
MAL	SMIM3	psi-mi:“MI:0915”(physical association)	0.720
MAL	FIBCD1	psi-mi:“MI:0915”(physical association)	0.720
SMIM3	MAL	psi-mi:“MI:0915”(physical association)	0.720
MAL	KLRC1	psi-mi:“MI:0915”(physical association)	0.720
MAL	STX1A	psi-mi:“MI:0915”(physical association)	0.600
MAL	CLEC4C	psi-mi:“MI:0915”(physical association)	0.600
MAL	PTPRN	psi-mi:“MI:0915”(physical association)	0.560
MAL	LSMEM1	psi-mi:“MI:0915”(physical association)	0.560
PTPRN	MAL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (86): MAL (Two-hybrid), MAL (Two-hybrid), PTPRN (Two-hybrid), FIBCD1 (Two-hybrid), SMIM3 (Two-hybrid), LSMEM1 (Two-hybrid), LDLRAD1 (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid), MAL (Two-hybrid)

ESM2 similar proteins: A2VE13, A4K2N5, A4K2W1, B8BPI2, E1BY51, O09117, O09198, O35682, O62646, O88662, O89104, P21145, Q04941, Q10EJ2, Q16563, Q1RMQ3, Q28296, Q3URJ8, Q3ZBY0, Q5R6H1, Q5RAI2, Q5VXT5, Q64349, Q6DHB5, Q6GPN9, Q6P0C6, Q6P742, Q6VBQ5, Q6Y1E2, Q78S06, Q86TG1, Q86UW1, Q8BI08, Q8CJ61, Q8IZ96, Q8IZR5, Q8N2H4, Q8N8D7, Q91WN2, Q95MN6

Diamond homologs: A2VE13, A3KQ86, O09198, P21145, Q13021, Q28296, Q3ZBY0, Q5RAI2, Q64349, Q6GPN9, Q8BI08, Q91X49, Q969L2, Q9CZR4, A6H7B0, P47987, Q1RMP9, Q8IZV2, Q9DCU2, Q9Y342

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SMO	“up-regulates quantity”	MAL	“transcriptional regulation”
MAL	up-regulates	Myelination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	15.3×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3362871	A109D	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:95049620:A:C	S101R	0.995
2:95049622:C:A	S101R	0.995
2:95049622:C:G	S101R	0.995
2:95047977:T:A	W38R	0.994
2:95047977:T:C	W38R	0.994
2:95048025:T:A	W54R	0.992
2:95048025:T:C	W54R	0.992
2:95049694:C:A	N125K	0.988
2:95049694:C:G	N125K	0.988
2:95053420:G:C	A143P	0.985
2:95048049:T:C	C62R	0.984
2:95049603:C:A	A95D	0.983
2:95047966:G:A	G34E	0.982
2:95049702:C:A	A128D	0.982
2:95047965:G:T	G34W	0.978
2:95047968:G:C	G35R	0.977
2:95048052:T:C	F63L	0.975
2:95048054:C:A	F63L	0.975
2:95048054:C:G	F63L	0.975
2:95049701:G:C	A128P	0.975
2:95047965:G:A	G34R	0.974
2:95047965:G:C	G34R	0.974
2:95048027:G:C	W54C	0.973
2:95048027:G:T	W54C	0.973
2:95048034:T:C	F57L	0.973
2:95048036:C:A	F57L	0.973
2:95048036:C:G	F57L	0.973
2:95047969:G:A	G35D	0.972
2:95048022:G:C	G53R	0.970
2:95049624:C:A	A102D	0.969

dbSNP variants (sampled 300 via entrez): RS1000067547 (2:95035901 C>A,T), RS1000267522 (2:95030348 CT>C), RS1000448196 (2:95030123 G>A,C), RS1000530031 (2:95053981 C>G), RS1000682959 (2:95048317 G>A), RS1000843630 (2:95034101 C>T), RS1001062411 (2:95034530 A>G), RS1001243700 (2:95042293 C>A,T), RS1001357455 (2:95051195 A>G), RS1001518289 (2:95037265 G>A,C), RS1001632447 (2:95044848 G>A,C), RS1001739075 (2:95037879 A>G), RS1001816448 (2:95044613 T>C), RS1001990428 (2:95025575 G>A), RS1002093331 (2:95026130 T>C)

Disease associations

OMIM: gene MIM:188860 | disease phenotypes: MIM:620978

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, hypomyelinating, 28	Moderate	Autosomal recessive

Mondo (1): leukodystrophy, hypomyelinating, 28 (MONDO:0975833)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001310	Dysmetria
HP:0001348	Brisk reflexes
HP:0002080	Intention tremor
HP:0002527	Falls
HP:0003593	Infantile onset
HP:0006895	Lower limb hypertonia
HP:0007266	Cerebral dysmyelination
HP:0033044	Motor regression

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	decreases methylation, increases expression	2
Estradiol	decreases expression, increases expression	2
Ethinyl Estradiol	affects expression	2
Cadmium Chloride	decreases expression, increases expression	2
tungsten carbide	decreases expression, affects binding	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
sulindac sulfide	decreases expression	1
pentanal	increases expression	1
rofecoxib	increases expression	1
lipopolysaccharide, Helicobacter pylori	increases expression, increases reaction	1
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	1
Irinotecan	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects response to substance	1
Cobalt	affects binding, decreases expression	1
Dietary Carbohydrates	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Ibuprofen	increases expression	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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