LETM2

Summary

LETM2 (leucine zipper and EF-hand containing transmembrane protein 2, HGNC:14648) is a protein-coding gene on chromosome 8p11.23, encoding LETM1 domain-containing protein LETM2, mitochondrial (Q2VYF4).

Predicted to enable transmembrane transporter activity. Predicted to be involved in mitochondrial calcium ion transmembrane transport and mitochondrion organization. Located in mitochondrion.

Source: NCBI Gene 137994 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 72 total
• GTEx eGene: eQTL in 7 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.25 (unconstrained)
• MANE Select transcript: NM_001286819
• Notable: 72 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14648
Approved symbol	LETM2
Name	leucine zipper and EF-hand containing transmembrane protein 2
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25409, SLC55A2
Ensembl gene	ENSG00000165046
Ensembl biotype	protein_coding
OMIM	620380
Entrez	137994

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000379957

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 5, TSL 3: 2, TSL 4: 2, TSL 5: 2

ENST00000379957, ENST00000297720, ENST00000518121, ENST00000518883, ENST00000519476, ENST00000523268, ENST00000523983, ENST00000524874, ENST00000526075, ENST00000526356, ENST00000527175, ENST00000527334, ENST00000527710, ENST00000528827, ENST00000530448, ENST00000889546, ENST00000948387, ENST00001138829

RefSeq mRNA: 9 — MANE Select: NM_001286819 NM_001199659, NM_001199660, NM_001286787, NM_001286819, NM_001286821, NM_001330515, NM_001363204, NM_001363205, NM_144652

CCDS: CCDS56534, CCDS6106, CCDS69466, CCDS75731, CCDS83282

Canonical transcript exons

ENST00000379957 — 11 exons

Exon	Start	End
ENSE00001527473	38394098	38394241
ENSE00001806127	38392542	38392995
ENSE00002122767	38386476	38386568
ENSE00003526354	38400272	38400409
ENSE00003526982	38400853	38401053
ENSE00003528064	38402525	38402644
ENSE00003536187	38407362	38407463
ENSE00003542896	38404393	38404506
ENSE00003589066	38406946	38407038
ENSE00003661105	38387950	38388030
ENSE00004793610	38408212	38409527

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 90.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7601 / max 249.4772, expressed in 1515 samples.

Highest expression (Bgee): testis, cerebellar hemisphere, cerebellar cortex, hemisphere of cerebellum, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LETM2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	2.9e-04	+1.75	8:38534635:C:T
Adrenal Gland	eqtl	1.1e-03	+0.27	8:38402922:C:T
Muscle Skeletal	eqtl	2.9e-03	-0.76	8:38767915:A:T
Heart Left Ventricle	eqtl	4.7e-03	-0.20	8:38923522:C:A
Esophagus Mucosa	sqtl	5.1e-03	+1.14	8:37693368:C:G
Cells Cultured fibroblasts	eqtl	1.4e-02	+0.09	8:38730795:G:A
Thyroid	eqtl	1.9e-02	-0.72	8:38114140:C:T
Small Intestine Terminal Ileum	eqtl	4.4e-02	-0.75	8:38545547:G:A
Cells EBV-transformed lymphocytes	eqtl	4.8e-02	+1.02	8:38424971:T:G

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
88490	4.5793	1280
88495	1.5223	414
88497	1.0469	312
88493	0.4509	198
88496	0.2946	112
88494	0.2878	129
88486	0.2632	95
88489	0.1522	53
88488	0.0929	39
88487	0.0484	24

Top tissues by expression

showing 100 of 239 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.16	gold quality
right testis	UBERON:0004534	89.49	gold quality
cerebellar hemisphere	UBERON:0002245	89.26	gold quality
cerebellar cortex	UBERON:0002129	89.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.85	gold quality
testis	UBERON:0000473	87.59	gold quality
cerebellum	UBERON:0002037	86.66	gold quality
secondary oocyte	CL:0000655	80.90	gold quality
islet of Langerhans	UBERON:0000006	78.05	gold quality
descending thoracic aorta	UBERON:0002345	77.30	gold quality
adenohypophysis	UBERON:0002196	76.01	gold quality
stromal cell of endometrium	CL:0002255	75.94	gold quality
cortical plate	UBERON:0005343	75.87	gold quality
oocyte	CL:0000023	75.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.70	gold quality
right coronary artery	UBERON:0001625	75.62	gold quality
left uterine tube	UBERON:0001303	75.61	gold quality
anterior cingulate cortex	UBERON:0009835	75.54	gold quality
leukocyte	CL:0000738	75.41	gold quality
body of pancreas	UBERON:0001150	75.39	gold quality
omental fat pad	UBERON:0010414	75.24	gold quality
right frontal lobe	UBERON:0002810	75.17	gold quality
peritoneum	UBERON:0002358	75.15	gold quality
granulocyte	CL:0000094	75.13	gold quality
pancreas	UBERON:0001264	75.00	gold quality
monocyte	CL:0000576	74.98	gold quality
thoracic aorta	UBERON:0001515	74.77	gold quality
ascending aorta	UBERON:0001496	74.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.26	gold quality
lower esophagus	UBERON:0013473	74.18	gold quality
pituitary gland	UBERON:0000007	74.17	gold quality
prefrontal cortex	UBERON:0000451	73.95	gold quality
aorta	UBERON:0000947	73.94	gold quality
hypothalamus	UBERON:0001898	73.90	gold quality
popliteal artery	UBERON:0002250	73.66	gold quality
tibial artery	UBERON:0007610	73.66	gold quality
metanephros cortex	UBERON:0010533	73.63	gold quality
amniotic fluid	UBERON:0000173	73.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.18	gold quality
calcaneal tendon	UBERON:0003701	73.14	gold quality
sperm	CL:0000019	72.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.49	gold quality
ventricular zone	UBERON:0003053	72.18	gold quality
ganglionic eminence	UBERON:0004023	72.17	gold quality
bone marrow cell	CL:0002092	72.09	gold quality
left coronary artery	UBERON:0001626	72.09	gold quality
mucosa of stomach	UBERON:0001199	72.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.88	gold quality
ectocervix	UBERON:0012249	71.87	gold quality
left ovary	UBERON:0002119	71.62	gold quality
blood	UBERON:0000178	71.60	gold quality
right atrium auricular region	UBERON:0006631	71.56	gold quality
nucleus accumbens	UBERON:0001882	71.51	gold quality
amygdala	UBERON:0001876	71.33	gold quality
right ovary	UBERON:0002118	71.27	gold quality
endocervix	UBERON:0000458	71.20	gold quality
caudate nucleus	UBERON:0001873	70.98	gold quality
tendon	UBERON:0000043	70.81	gold quality
cardiac atrium	UBERON:0002081	70.76	gold quality
coronary artery	UBERON:0001621	70.65	gold quality
putamen	UBERON:0001874	70.57	gold quality
esophagus	UBERON:0001043	70.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.48	gold quality
right uterine tube	UBERON:0001302	70.38	gold quality
gall bladder	UBERON:0002110	70.17	gold quality
upper lobe of left lung	UBERON:0008952	70.16	gold quality
neocortex	UBERON:0001950	70.15	gold quality
body of uterus	UBERON:0009853	69.83	gold quality
brain	UBERON:0000955	69.50	gold quality
ovary	UBERON:0000992	69.43	gold quality
heart left ventricle	UBERON:0002084	69.35	gold quality
adrenal tissue	UBERON:0018303	69.10	gold quality
spinal cord	UBERON:0002240	69.01	gold quality
frontal cortex	UBERON:0001870	68.93	gold quality
body of stomach	UBERON:0001161	68.85	gold quality
upper lobe of lung	UBERON:0008948	68.80	gold quality
apex of heart	UBERON:0002098	68.63	gold quality
heart	UBERON:0000948	68.47	gold quality
right lung	UBERON:0002167	68.45	gold quality
smooth muscle tissue	UBERON:0001135	68.42	gold quality
cardiac ventricle	UBERON:0002082	68.37	gold quality
adult mammalian kidney	UBERON:0000082	68.18	gold quality
forebrain	UBERON:0001890	67.87	gold quality
tibial nerve	UBERON:0001323	67.85	gold quality
buccal mucosa cell	CL:0002336	67.64	silver quality
esophagus mucosa	UBERON:0002469	67.58	gold quality
vagina	UBERON:0000996	67.34	gold quality
cortex of kidney	UBERON:0001225	67.29	gold quality
tendon of biceps brachii	UBERON:0008188	67.14	gold quality
stomach	UBERON:0000945	66.98	gold quality
cerebral cortex	UBERON:0000956	66.97	gold quality
anatomical system	UBERON:0000467	66.87	gold quality
lower esophagus mucosa	UBERON:0035834	66.76	gold quality
uterine cervix	UBERON:0000002	66.68	gold quality
transverse colon	UBERON:0001157	66.52	gold quality
material anatomical entity	UBERON:0000465	66.40	gold quality
multicellular organism	UBERON:0000468	66.39	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	32.2	not detected
Testis	tissue	22.2	high
Postcentral gyrus	tissue	11.9
Choroid plexus	tissue	10.6
Nucleus accumbens	tissue	10.2
Locus coeruleus	tissue	9.9
Hippocampus	tissue	8.1	not detected
Hippocampal formation	tissue	5.7
Pons	tissue	5.2
Bone marrow	tissue	5.0	not detected
Periaqueductal gray	tissue	4.8
Spinal cord	tissue	4.7
Hypothalamus	tissue	4.6
Amygdala	tissue	4.5
Frontal cortex	tissue	4.4
Medulla oblongata	tissue	4.4
Caudate putamen	tissue	4.4
Midbrain	tissue	4.2
Corpus callosum	tissue	4.1
Septum	tissue	4.0
Retina	tissue	3.9
Substantia nigra	tissue	3.9
Basal ganglia	tissue	3.7	not detected
Superior colliculi	tissue	3.7
Thalamus	tissue	3.6
Ventral forebrain	tissue	3.5
Cerebral cortex	tissue	3.2	not detected
Olfactory bulb	tissue	3.2
Insular cortex	tissue	3.2
Entorhinal cortex	tissue	3.1
Retrosplenial cortex	tissue	3.1
Putamen	tissue	3.0
Prefrontal cortex	tissue	2.9
Motor cortex	tissue	2.9
Temporal cortex	tissue	2.9
Retrosplenial and cingulate cortex	tissue	2.8
Stomach 1	tissue	2.5	medium
Somatosensory cortex	tissue	2.5
Occipital cortex	tissue	2.4
Kidney	tissue	2.2	not detected
Thymus	tissue	2.2
Pituitary gland	tissue	2.1
Lung	tissue	1.9	not detected
Urinary bladder	tissue	1.8	not detected
Placenta	tissue	1.7	medium
Cervix	tissue	1.5	low
Ovary	tissue	1.5	low
Parathyroid gland	tissue	1.5	not detected
Spleen	tissue	1.5	not detected
Endometrium 1	tissue	1.3	medium
Tonsil	tissue	1.3	medium
Fallopian tube	tissue	1.3	medium
Lymph node	tissue	1.2	not detected
Esophagus	tissue	1.1	not detected
Gallbladder	tissue	1.1	medium
Skin 1	tissue	1.0	not detected
Epididymis	tissue	1.0	medium
Prostate	tissue	1.0
Adrenal gland	tissue	1.0	not detected
Appendix	tissue	1.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Flocculonodular lobe (16.0), Vermis (14.5), Cerebellar cortex (14.3), Parieto-temporal junction (white matter) (13.1), Corpus callosum, splenium (white matter) (13.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LETM2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 46 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-140-3P	99.04	67.69	1324

Functional genomics

gnomAD constraint: pLI 7e-12, LOEUF 1.25, missense Z 0.316 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000379957 — one region, missense o/e 0.99.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	letm2	ENSDARG00000077515
mus_musculus	Letm2	ENSMUSG00000037363
rattus_norvegicus	Letm2	ENSRNOG00000026180

Paralogs (2): LETMD1 (ENSG00000050426), LETM1 (ENSG00000168924)

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	Q0VCA3	79.2%	Diamond
Gallus gallus	Q5ZK33	72.3%	Diamond
Xenopus tropicalis	Q0VA06	71.8%	Diamond
Saccharomyces cerevisiae S288C	Q06493	50.3%	Diamond
Drosophila melanogaster	P91927	50.0%	Diamond
Schizosaccharomyces pombe 972h-	O13920	47.5%	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
FGFR1	protein-coding	2260
DDHD2	protein-coding	23259
LINC03042	ncRNA	389649
NSD3	protein-coding	54904
PLPP5	protein-coding	84513
BAG4	protein-coding	9530
LSM1	protein-coding	27257

Protein

Protein identifiers

LETM1 domain-containing protein LETM2, mitochondrial — Q2VYF4 (reviewed: Q2VYF4)

Alternative names: LETM1 and EF-hand domain-containing protein 2, Leucine zipper-EF-hand-containing transmembrane protein 1-like

All UniProt accessions (8): Q2VYF4, A8K1M9, E5RJN4, E5RK40, E9PIC7, E9PMA4, E9PN52, H0YCZ8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Mitochondrion inner membrane.

Isoforms (4)

UniProt ID	Names	Canonical?
Q2VYF4-1	1	yes
Q2VYF4-2	2
Q2VYF4-3	3
Q2VYF4-4	4

RefSeq proteins (9): NP_001186588, NP_001186589, NP_001273716, NP_001273748, NP_001273750, NP_001317444, NP_001350133, NP_001350134, NP_653253 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033122	LETM1-like_RBD	Domain
IPR044202	LETM1/MDM38-like	Family
IPR045742	LETM2_N	Domain

Pfam: PF07766, PF19324

UniProt features (17 total): splice variant 4, compositionally biased region 3, topological domain 2, region of interest 2, transit peptide 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2VYF4-F1	62.77	0.15

Human Protein Atlas

Protein class: Transporters, Electrochemical Potential-driven transporters, Predicted membrane proteins, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; nuclear bodies

Antibody reliability (HPA): IH approved · IF approved

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: 106 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, SHEPARD_BMYB_MORPHOLINO_UP, CREBP1_Q2, GOBP_MONOATOMIC_CATION_TRANSPORT, CREB_Q4, E4F1_Q6, GOCC_MITOCHONDRIAL_ENVELOPE, AACTTT_UNKNOWN, SENESE_HDAC1_TARGETS_UP, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_ORGANELLE_INNER_MEMBRANE, MARSON_BOUND_BY_FOXP3_STIMULATED, YATGNWAAT_OCT_C, GOMF_RIBONUCLEOPROTEIN_COMPLEX_BINDING

GO Biological Process (2): mitochondrial calcium ion transmembrane transport (GO:0006851), mitochondrion organization (GO:0007005)

GO Molecular Function (2): transmembrane transporter activity (GO:0022857), ribosome binding (GO:0043022)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743)

GO top-level categories

9 GO namespaces:

Category	Terms
calcium ion transmembrane transport	1
organelle organization	1
transporter activity	1
transmembrane transport	1
ribonucleoprotein complex binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 6 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrion	CC	high-throughput

Protein interactions and networks

STRING

showing 15 of 891 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LETM2	GOT1L1	Q8NHS2	615
LETM2	RAB11FIP1	Q6WKZ4	573
LETM2	BRF2	Q9HAW0	544
LETM2	NSD3	Q9BZ95	507
LETM2	DDHD2	O94830	502
LETM2	PLPP5	Q8NEB5	470
LETM2	SIRAL2	Q9NWS6	469
LETM2	RHBDD3	Q9Y3P4	460
LETM2	EIF4EBP1	Q13541	459
LETM2	DNAJC18	Q9H819	458
LETM2	PLPBP	O94903	453
LETM2	TTC39C	Q8N584	438
LETM2	REEP6	Q96HR9	437
LETM2	TMEM39B	Q9GZU3	436
LETM2	MICU1	Q9BPX6	432

IntAct

Human interaction partners of LETM2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
EIF3CL	association	0.350	1
GAPDHS	association	0.350	1
LETM1	association	0.350	1

BioGRID (78 interactions; top human partners by supporting records): AHNAK (Affinity Capture-MS), AK4 (Affinity Capture-MS), AMOT (Affinity Capture-MS), AP2A2 (Affinity Capture-MS), APMAP (Affinity Capture-MS), APP (Reconstituted Complex), ARL6IP5 (Affinity Capture-MS), ARPC4 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), BCS1L (Affinity Capture-MS), BRD2 (Affinity Capture-MS), BRD3 (Affinity Capture-MS), BRD4 (Affinity Capture-MS), C14orf1 (Affinity Capture-MS), C17orf49 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for LETM2: 72 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,137):

Position(s)	Effect	Δscore	Sites
8:38402523	acceptor_loss	1.0000	2
8:38402645	donor_loss	1.0000	3
8:38404383	acceptor_gain	1.0000
8:38404391–38404392	acceptor_loss	1.0000	6
8:38404507–38404508	donor_loss	1.0000	2
8:38405405	donor_gain	1.0000
8:38406944–38406945	acceptor_loss	1.0000	5
8:38407039–38407040	donor_loss	1.0000	5
8:38394129	acceptor_gain	0.9900
8:38400846	acceptor_gain	0.9900

AlphaMissense

500 missense substitutions predicted likely pathogenic (of 3,191 scored), across 171 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
D327	8	0.950	0.985
D174	8	0.872	0.942
F209	8	0.846	0.974
F280	8	0.837	0.951
D143	8	0.785	0.903
W369	7	0.967	0.994
F232	7	0.867	0.977
M352	7	0.861	0.980
F184	7	0.830	0.930
D326	7	0.826	0.924
F201	7	0.825	0.935
E342	7	0.749	0.895
E191	7	0.744	0.871
G351	6	0.897	0.962
P206	6	0.826	0.943
P188	6	0.821	0.919
R162	6	0.819	0.914
F314	6	0.811	0.928
P180	6	0.798	0.934
E164	6	0.782	0.922

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	2.21e-05
Glioblastoma Multiforme (TCGA)	unfavorable	7.45e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	7.97e-05

Disease associations

OMIM: gene MIM:620380 | disease phenotypes:

GWAS associations

12 associations:

Study	Trait	p-value
GCST90000025_909	Appendicular lean mass	1e-21
GCST90002387_200	Immature fraction of reticulocytes	8e-15
GCST90002388_529	Lymphocyte count	8e-15
GCST007201_191	Schizophrenia	1e-12
GCST004946_26	Schizophrenia	1e-11
GCST007269_99	Pulse pressure	2e-11
GCST006803_57	Schizophrenia	6e-10
GCST009600_105	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2e-9
GCST004521_143	Autism spectrum disorder or schizophrenia	4e-9
GCST007201_258	Schizophrenia	1e-6
GCST003469_12	Response to cognitive-behavioural therapy in anxiety disorder	4e-6
GCST008103_157	Bipolar disorder	7e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0005763	pulse pressure measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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
(+)-JQ1 compound	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression	2
Smoke	decreases expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Theophylline	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	increases expression	1
Aflatoxin B1	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4G1	HCT116-LETM2-KO-c11	Cancer cell line	Male
CVCL_D4G2	HCT116-LETM2-KO-c2	Cancer cell line	Male

Clinical trials (associated diseases)

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