LETMD1

Summary

LETMD1 (LETM1 domain containing 1, HGNC:24241) is a protein-coding gene on chromosome 12q13.12, encoding LETM1 domain-containing protein 1 (Q6P1Q0). Plays an essential role for mitochondrial structure and function, as well as thermogenesis of brown adipocytes.

This gene encodes a mitochondrial outer membrane protein. It has a potential role in tumorigenesis, which may result from negative regulation of the p53 tumor suppressor gene. Alternatively spliced transcript variants have been noted for this gene.

Source: NCBI Gene 25875 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_015416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24241
Approved symbol	LETMD1
Name	LETM1 domain containing 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	HCCR1, HCCR, HCCR-2, HCCR-1, HCCR2, SLC55A3
Ensembl gene	ENSG00000050426
Ensembl biotype	protein_coding
OMIM	619070
Entrez	25875

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 40 protein_coding, 8 retained_intron, 7 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined, 1 TEC

ENST00000262055, ENST00000380135, ENST00000418425, ENST00000546814, ENST00000546992, ENST00000547008, ENST00000547029, ENST00000547256, ENST00000547318, ENST00000547555, ENST00000547660, ENST00000547877, ENST00000548209, ENST00000548251, ENST00000548390, ENST00000548401, ENST00000548516, ENST00000549340, ENST00000549395, ENST00000549686, ENST00000550100, ENST00000550274, ENST00000550442, ENST00000550446, ENST00000550715, ENST00000550755, ENST00000550814, ENST00000550929, ENST00000551261, ENST00000551477, ENST00000551931, ENST00000552430, ENST00000552433, ENST00000552645, ENST00000552739, ENST00000553043, ENST00000553175, ENST00000623495, ENST00000882982, ENST00000882983, ENST00000882984, ENST00000882985, ENST00000882986, ENST00000882987, ENST00000882988, ENST00000882989, ENST00000926718, ENST00000926719, ENST00000926720, ENST00000926721, ENST00000926722, ENST00000926723, ENST00000926724, ENST00000926725, ENST00000926726, ENST00000949997, ENST00000949998, ENST00000950000, ENST00000950002, ENST00000950003, ENST00000950004, ENST00000950005

RefSeq mRNA: 25 — MANE Select: NM_015416 NM_001243689, NM_001300765, NM_001351312, NM_001351313, NM_001351315, NM_001351316, NM_001351317, NM_001351319, NM_001351320, NM_001351321, NM_001351322, NM_001351323, NM_001351324, NM_001351325, NM_001351326, NM_001351327, NM_001351328, NM_001351330, NM_001351332, NM_001351333, NM_001351334, NM_001351335, NM_001351336, NM_001351337, NM_015416

CCDS: CCDS44883, CCDS58231, CCDS73469, CCDS86301, CCDS8806

Canonical transcript exons

ENST00000262055 — 9 exons

Exon	Start	End
ENSE00003481388	51058032	51058128
ENSE00003500251	51049034	51049185
ENSE00003510292	51048327	51048478
ENSE00003570662	51055835	51056021
ENSE00003579462	51056144	51056245
ENSE00003605082	51053778	51053860
ENSE00003611934	51056350	51056502
ENSE00003677678	51052092	51052207
ENSE00003679164	51059361	51060424

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.0450 / max 322.6012, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125473	57.9406	1822
125474	0.1043	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.71	gold quality
right uterine tube	UBERON:0001302	97.02	gold quality
rectum	UBERON:0001052	96.84	gold quality
left ovary	UBERON:0002119	96.54	gold quality
metanephros cortex	UBERON:0010533	96.53	gold quality
cortical plate	UBERON:0005343	96.44	gold quality
left lobe of thyroid gland	UBERON:0001120	96.30	gold quality
right lobe of thyroid gland	UBERON:0001119	96.29	gold quality
body of stomach	UBERON:0001161	96.24	gold quality
right ovary	UBERON:0002118	96.15	gold quality
right adrenal gland cortex	UBERON:0035827	96.01	gold quality
mucosa of stomach	UBERON:0001199	95.95	gold quality
transverse colon	UBERON:0001157	95.93	gold quality
thyroid gland	UBERON:0002046	95.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.91	gold quality
pancreas	UBERON:0001264	95.90	gold quality
right adrenal gland	UBERON:0001233	95.79	gold quality
minor salivary gland	UBERON:0001830	95.73	gold quality
endocervix	UBERON:0000458	95.64	gold quality
left adrenal gland cortex	UBERON:0035825	95.54	gold quality
left adrenal gland	UBERON:0001234	95.51	gold quality
body of uterus	UBERON:0009853	95.50	gold quality
skin of leg	UBERON:0001511	95.44	gold quality
skin of abdomen	UBERON:0001416	95.38	gold quality
adenohypophysis	UBERON:0002196	95.37	gold quality
stomach	UBERON:0000945	95.36	gold quality
ectocervix	UBERON:0012249	95.30	gold quality
small intestine	UBERON:0002108	95.20	gold quality
pituitary gland	UBERON:0000007	95.18	gold quality
adrenal cortex	UBERON:0001235	95.00	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting LETMD1, 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-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-4637	97.69	68.14	632
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-9851-5P	97.57	67.49	1067

Literature-anchored findings (GeneRIF, showing 24)

• Human, similar to bacterial ribosomal protein L14 and yeast L22, gene L14.22 (clone 507E08), over-expressed in gliomas. (PMID:12061725)
• HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor (PMID:12879013)
• HCCR-2 represents an oncoprotein that is related to breast cancer development and regulation of the p53 tumor suppressor. (PMID:14691448)
• HCCR oncoprotein has a role in development of human breast cancer (PMID:16278390)
• These results suggest that the HCCR-1 oncogene expression was regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway. (PMID:16949218)
• These experiments show the biological features of HCCR-1 in the cell, and suggest that uncontrolled expression of HCCR-1 may cause mitochondrial dysfunction. (PMID:18045496)
• Data indicate that the level of HCCR-1 in breast cancer tissues is correlated with the HER2 overexpression, p53 mutation, and ER/PR status, and determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation. (PMID:19208263)
• TCF and beta-catenin binding plays important roles in HCCR-1 oncogene expression. (PMID:19435525)
• HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE (PMID:20196787)
• Treatment of PANC-1 cells with epidermal growth factor increased HCCR-1 protein level via PI3K/Akt/mTOR signaling. (PMID:20423485)
• induces neoplastic cell transformation and epithelial-mesenchymal transdifferentiation (PMID:20591135)
• The overexpression of HCCR-2 could enhance the division and proliferation of SMMC 7721 cells. (PMID:21138632)
• The data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with esophageal squamous cell carcinoma. (PMID:22511601)
• HCCRBP-3 induces tumorigenesis through direct interaction with HCCR-1 in human cancers. (PMID:22851403)
• HCCR2 gene plays an important role in the tumorigenesis of leukemia. (PMID:24126909)
• These findings suggest that HCCR gene is over-expressed in acute leukemia patients and may be a useful biomarker for monitoring minimal residual disease. (PMID:25034723)
• Demonstrate that HBx-HCCR-E-cadherin regulation pathway might play an important role in HBV-induced hepatocarcinogenesis. (PMID:26470691)
• Data show that the activation of STAT3 protein upregulated human cervical cancer oncogene (HCCR) expression in gastric cancer cells. (PMID:27052330)
• HCCR-1 siRNA transfection causes significant increase in the apoptosis and decreases in the proliferation of MCF-7 cellsThese effects are related to the upregulation of the Bax expression in the MCF-7 cells. (PMID:31424657)
• LETMD1 Regulates Phagocytosis and Inflammatory Responses to Lipopolysaccharide via Reactive Oxygen Species Generation and NF-kappaB Activation in Macrophages. (PMID:31980577)
• Knockdown of SNHG1 inhibits cervical cancer growth through sponging miR-194 to regulate HCCR. (PMID:32456490)
• The regulating role of miR-494 on HCCR1 in cervical cancer cells. (PMID:35818261)
• MiR-494 Inhibits the Proliferation, Migration and Invasion of Cervical Cancer Cells by Regulating LETMD1. (PMID:35818268)
• LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis: A protective mechanism in the pathogenesis of atherosclerosis. (PMID:37769890)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	letmd1	ENSDARG00000030641
mus_musculus	Letmd1	ENSMUSG00000037353
rattus_norvegicus	Letmd1	ENSRNOG00000029855
drosophila_melanogaster	CG5989	FBGN0017429
caenorhabditis_elegans	F30F8.9	WBGENE00009276

Paralogs (2): LETM2 (ENSG00000165046), LETM1 (ENSG00000168924)

Protein

Protein identifiers

LETM1 domain-containing protein 1 — Q6P1Q0 (reviewed: Q6P1Q0)

Alternative names: Cervical cancer 1 proto-oncogene protein p40, Cervical cancer proto-oncogene 2 protein, HCCR-1, HCRR-2

All UniProt accessions (21): A0A384P5D7, Q6P1Q0, F8VP71, F8VPY5, F8VQE7, F8VR33, F8VR35, F8VS60, F8VTR1, F8VUZ8, F8VVQ3, F8VXQ4, F8VZA2, F8W0R0, F8W1U1, F8W1Z2, F8W6J0, F8WCD9, H0YH93, H0YHF4, H0YIV5

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role for mitochondrial structure and function, as well as thermogenesis of brown adipocytes. In brown adipose tissue also localizes in the nucleus where it interacts with the chromatin remodeler SMARCA4 to regulate thermogenic genes expression, such as UCP1. May regulate phagocytosis and inflammatory responses to lipopolysaccharide in macrophages. Involved in tumorigenesis and may function as a negative regulator of the p53/TP53.

Subunit / interactions. Interacts with BRI3BP. Interacts (via C-terminal) with SMARCA4; the interaction regulates transcriptional expression of thermogenic genes in brown adipose tissue.

Subcellular location. Mitochondrion outer membrane. Nucleus. Mitochondrion inner membrane.

Tissue specificity. Kidney, liver, skeletal muscle, heart and brain. Overexpressed in various tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon and uterine cervix.

Isoforms (7)

UniProt ID	Names	Canonical?
Q6P1Q0-1	1, HCCR-1	yes
Q6P1Q0-2	2, HCRR-2
Q6P1Q0-3	3
Q6P1Q0-4	4
Q6P1Q0-5	5
Q6P1Q0-6	6
Q6P1Q0-7	7

RefSeq proteins (25): NP_001230618, NP_001287694, NP_001338241, NP_001338242, NP_001338244, NP_001338245, NP_001338246, NP_001338248, NP_001338249, NP_001338250, NP_001338251, NP_001338252, NP_001338253, NP_001338254, NP_001338255, NP_001338256, NP_001338257, NP_001338259, NP_001338261, NP_001338262, NP_001338263, NP_001338264, NP_001338265, NP_001338266, NP_056231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033122	LETM1-like_RBD	Domain
IPR044202	LETM1/MDM38-like	Family

Pfam: PF07766

UniProt features (16 total): splice variant 8, topological domain 2, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1Q0-F1	81.53	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): GOBP_INFLAMMATORY_RESPONSE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, CCANNAGRKGGC_UNKNOWN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN

GO Biological Process (14): ATP biosynthetic process (GO:0006754), phagocytosis (GO:0006909), inflammatory response (GO:0006954), mitochondrion organization (GO:0007005), response to lipopolysaccharide (GO:0032496), toll-like receptor 4 signaling pathway (GO:0034142), non-canonical NF-kappaB signal transduction (GO:0038061), transcription initiation-coupled chromatin remodeling (GO:0045815), regulation of inflammatory response (GO:0050727), regulation of phagocytosis (GO:0050764), mitochondrial calcium ion homeostasis (GO:0051560), positive regulation of cold-induced thermogenesis (GO:0120162), reactive oxygen species biosynthetic process (GO:1903409), gene expression (GO:0010467)

GO Molecular Function (3): ribosome binding (GO:0043022), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
mitochondrial membrane	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
endocytosis	1
defense response	1
organelle organization	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
cell surface toll-like receptor signaling pathway	1
intracellular signaling cassette	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
phagocytosis	1
regulation of endocytosis	1
mitochondrion	1
intracellular calcium ion homeostasis	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
biosynthetic process	1
reactive oxygen species metabolic process	1
macromolecule biosynthetic process	1
ribonucleoprotein complex binding	1
molecular_function	1
intracellular membraneless organelle	1
cytoplasm	1
organelle outer membrane	1
organelle inner membrane	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LETMD1	TP53	P04637	524
LETMD1	SMARCC2	Q8TAQ2	495
LETMD1	MYC	P01106	440
LETMD1	ARID1B	Q8NFD5	431
LETMD1	AFP	P02771	430
LETMD1	UBXN1	Q04323	388
LETMD1	LMBR1	Q8WVP7	380
LETMD1	TEX35	Q5T0J7	378
LETMD1	ALDH18A1	P54886	377
LETMD1	RPL14	P50914	374
LETMD1	CSDC2	Q9Y534	369
LETMD1	PJA2	O43164	334
LETMD1	SF3B5	Q9BWJ5	326
LETMD1	TFAP2E	Q6VUC0	326
LETMD1	ADISSP	Q9GZN8	325

IntAct

107 interactions, top by confidence:

A	B	Type	Score
LETMD1	RTN4IP1	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
LETMD1	REEP5	psi-mi:“MI:0915”(physical association)	0.580
APOC1	LETMD1	psi-mi:“MI:0915”(physical association)	0.560
APOC4	LETMD1	psi-mi:“MI:0915”(physical association)	0.560
LETMD1	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
RHBDD2	LETMD1	psi-mi:“MI:0915”(physical association)	0.560
NRAS	RGL2	psi-mi:“MI:0914”(association)	0.550
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LETMD1	BRI3BP	psi-mi:“MI:0915”(physical association)	0.520
SH2D1A	LETMD1	psi-mi:“MI:0915”(physical association)	0.370
HCK	LETMD1	psi-mi:“MI:0915”(physical association)	0.370
LETMD1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
Rab5b	XPO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): LETMD1 (Affinity Capture-RNA), LETMD1 (Affinity Capture-RNA), LETMD1 (Affinity Capture-RNA), LETMD1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), CPVL (Affinity Capture-MS), RTN4IP1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), LETMD1 (Two-hybrid), LETMD1 (Two-hybrid), LETMD1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS), LETMD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIJ0, A1L1L2, A3KN46, A4FV45, A9ULG4, B1H1N7, O95202, P0C1Q3, P0DKR2, P82933, Q0VCA3, Q149M9, Q14CZ7, Q1LXZ7, Q28EM8, Q2TBP8, Q3B8B2, Q3SZK4, Q3U2U7, Q4V8A1, Q58CX2, Q5M9G9, Q5PQQ5, Q5T197, Q5T1A1, Q5XIN6, Q5ZJY9, Q640M6, Q66JZ4, Q6DJ55, Q6NUQ4, Q6P1Q0, Q6PA48, Q6PBN5, Q6ZQE4, Q7TNU7, Q7YS91, Q810S1, Q86VS3, Q8BM55

Diamond homologs: A3KN46, Q28EM8, Q6P1Q0, Q924L1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
Metal ion SLC transporters	5	46.2×	8e-06
R-HSA-425366	5	13.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	39.5×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1670 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51053861:G:GG	donor_gain	1.0000
12:51056333:ATGT:A	acceptor_gain	1.0000
12:51056333:ATGTG:A	acceptor_gain	1.0000
12:51056334:T:G	acceptor_gain	1.0000
12:51056336:T:TA	acceptor_gain	1.0000
12:51056348:A:AG	acceptor_gain	1.0000
12:51056349:G:GG	acceptor_gain	1.0000
12:51056491:G:GT	donor_gain	1.0000
12:51056503:GTA:G	donor_loss	1.0000
12:51056504:T:G	donor_loss	1.0000
12:51048371:G:GT	donor_gain	0.9900
12:51049182:AAAGG:A	donor_loss	0.9900
12:51049183:AAG:A	donor_loss	0.9900
12:51049186:GTAA:G	donor_loss	0.9900
12:51049187:T:A	donor_loss	0.9900
12:51053776:A:AG	acceptor_gain	0.9900
12:51053777:G:GG	acceptor_gain	0.9900
12:51056333:AT:A	acceptor_gain	0.9900
12:51056337:G:A	acceptor_gain	0.9900
12:51056342:T:TA	acceptor_gain	0.9900
12:51056345:TACA:T	acceptor_loss	0.9900
12:51056349:G:A	acceptor_loss	0.9900
12:51056349:GA:G	acceptor_gain	0.9900
12:51056349:GAA:G	acceptor_gain	0.9900
12:51056349:GAAA:G	acceptor_gain	0.9900
12:51056403:G:GC	acceptor_gain	0.9900
12:51056491:G:T	donor_gain	0.9900
12:51056498:AATCG:A	donor_gain	0.9900
12:51056499:ATCG:A	donor_gain	0.9900
12:51056500:TCG:T	donor_gain	0.9900

AlphaMissense

2338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51058101:T:A	W329R	0.981
12:51058101:T:C	W329R	0.981
12:51058044:C:A	R310S	0.980
12:51055896:T:C	F179L	0.979
12:51055898:C:A	F179L	0.979
12:51055898:C:G	F179L	0.979
12:51056447:A:C	D287A	0.967
12:51056447:A:T	D287V	0.967
12:51049185:G:A	G92R	0.966
12:51049185:G:C	G92R	0.966
12:51056446:G:C	D287H	0.965
12:51053799:T:C	C138R	0.963
12:51053836:C:A	A150D	0.959
12:51055869:T:C	F170L	0.959
12:51055871:C:A	F170L	0.959
12:51055871:C:G	F170L	0.959
12:51056198:T:C	F239L	0.958
12:51056200:C:A	F239L	0.958
12:51056200:C:G	F239L	0.958
12:51058037:T:G	C307W	0.957
12:51058103:G:C	W329C	0.951
12:51058103:G:T	W329C	0.951
12:51055872:T:A	W171R	0.949
12:51055872:T:C	W171R	0.949
12:51058035:T:C	C307R	0.949
12:51053848:T:A	V154D	0.947
12:51053812:G:A	G142D	0.946
12:51056444:T:C	L286P	0.946
12:51055874:G:C	W171C	0.945
12:51055874:G:T	W171C	0.945

dbSNP variants (sampled 300 via entrez): RS1000024743 (12:51054239 A>G), RS1000027599 (12:51050803 C>G,T), RS1000087982 (12:51052851 A>G), RS1000150513 (12:51048169 T>C,G), RS1000178264 (12:51055110 C>A), RS1000481666 (12:51054827 G>A), RS1000520591 (12:51056460 A>G), RS1000649031 (12:51054504 C>T), RS1000818682 (12:51056154 G>T), RS1001322862 (12:51066501 C>A), RS1001391367 (12:51068404 G>A), RS1001538716 (12:51062336 T>A,C), RS1001548570 (12:51061160 C>T), RS1001888788 (12:51063651 G>A,T), RS1001995816 (12:51055793 G>A)

Disease associations

OMIM: gene MIM:619070 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC55 Mitochondrial cation/proton exchangers

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
bisphenol A	increases methylation, decreases reaction, increases abundance, decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, affects expression, decreases expression, increases abundance	2
Acrolein	affects cotreatment, affects expression, decreases expression, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, affects expression, increases abundance	2
Ozone	affects cotreatment, affects expression, decreases expression, increases abundance	2
Tunicamycin	increases expression	2
afuresertib	increases expression	1
ginger extract	increases expression, decreases reaction, increases abundance	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
lead acetate	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	increases expression	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4G3	HCT116-LETMD1-KO-c11	Cancer cell line	Male
CVCL_D4G4	HCT116-LETMD1-KO-c7	Cancer cell line	Male
CVCL_SV46	HAP1 LETMD1 (-) 1	Cancer cell line	Male
CVCL_XQ11	HAP1 LETMD1 (-) 2	Cancer cell line	Male
CVCL_XQ12	HAP1 LETMD1 (-) 3	Cancer cell line	Male
CVCL_XQ13	HAP1 LETMD1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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