SLC25A44

Summary

SLC25A44 (solute carrier family 25 member 44, HGNC:29036) is a protein-coding gene on chromosome 1q22, encoding Solute carrier family 25 member 44 (Q96H78). Mitochondrial solute transporter which transports branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria in brown adipose tissue (BAT).

SLC25A44 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).

Source: NCBI Gene 9673 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_014655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29036
Approved symbol	SLC25A44
Name	solute carrier family 25 member 44
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90431, KIAA0446
Ensembl gene	ENSG00000160785
Ensembl biotype	protein_coding
OMIM	610824
Entrez	9673

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000359511, ENST00000423538, ENST00000468973, ENST00000469537, ENST00000482737, ENST00000684582, ENST00000882957, ENST00000882958, ENST00000882959, ENST00000882960, ENST00000882961, ENST00000882962, ENST00000926780, ENST00000926781, ENST00000960306

RefSeq mRNA: 8 — MANE Select: NM_014655 NM_001286184, NM_001377385, NM_001377386, NM_001377387, NM_001377388, NM_001377389, NM_001377390, NM_014655

CCDS: CCDS1133, CCDS72943

Canonical transcript exons

ENST00000359511 — 4 exons

Exon	Start	End
ENSE00001416037	156199835	156200472
ENSE00001890172	156210240	156212796
ENSE00001946427	156194104	156194247
ENSE00003668866	156207886	156208013

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 91.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2377 / max 163.6229, expressed in 1803 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5701	16.2377	1803

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	91.45	gold quality
blood	UBERON:0000178	90.50	gold quality
tendon of biceps brachii	UBERON:0008188	90.20	silver quality
medial globus pallidus	UBERON:0002477	89.75	silver quality
right frontal lobe	UBERON:0002810	89.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.45	silver quality
islet of Langerhans	UBERON:0000006	89.28	gold quality
right lobe of liver	UBERON:0001114	89.27	gold quality
frontal cortex	UBERON:0001870	89.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.87	gold quality
neocortex	UBERON:0001950	88.79	gold quality
anterior cingulate cortex	UBERON:0009835	88.66	gold quality
globus pallidus	UBERON:0001875	88.65	silver quality
cingulate cortex	UBERON:0003027	88.64	gold quality
granulocyte	CL:0000094	88.60	gold quality
adult mammalian kidney	UBERON:0000082	88.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.56	gold quality
secondary oocyte	CL:0000655	87.86	gold quality
cortical plate	UBERON:0005343	87.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.70	gold quality
oocyte	CL:0000023	87.52	gold quality
colonic epithelium	UBERON:0000397	87.48	gold quality
cerebellar cortex	UBERON:0002129	87.45	gold quality
liver	UBERON:0002107	87.44	gold quality
cerebellar hemisphere	UBERON:0002245	87.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.44	gold quality
cerebral cortex	UBERON:0000956	87.29	gold quality
inferior olivary complex	UBERON:0002127	87.24	gold quality
metanephros cortex	UBERON:0010533	87.03	gold quality
substantia nigra pars compacta	UBERON:0001965	86.98	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	385.21
E-MTAB-6142	no	245.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting SLC25A44, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-6721-5P	99.93	68.92	2981

Literature-anchored findings (GeneRIF, showing 3)

• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• The GBA-370Rec Parkinson’s disease risk haplotype harbors a potentially pathogenic variant in the mitochondrial gene SLC25A44. (PMID:33762134)
• Genome Evolutionary Dynamics Meets Functional Genomics: A Case Story on the Identification of SLC25A44. (PMID:34073512)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a44b	ENSDARG00000035905
danio_rerio	slc25a44a	ENSDARG00000045927
mus_musculus	Slc25a44	ENSMUSG00000050144
rattus_norvegicus	Slc25a44	ENSRNOG00000025269
drosophila_melanogaster	CG5805	FBGN0039223
caenorhabditis_elegans	F13G3.7	WBGENE00008767

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), SLC25A11 (ENSG00000108528), UCP1 (ENSG00000109424), SLC25A36 (ENSG00000114120), SLC25A12 (ENSG00000115840), SLC25A2 (ENSG00000120329), SLC25A51 (ENSG00000122696), SLC25A16 (ENSG00000122912), SLC25A35 (ENSG00000125434), SLC25A19 (ENSG00000125454), SLC25A23 (ENSG00000125648), SLC25A47 (ENSG00000140107), SLC25A52 (ENSG00000141437), SLC25A38 (ENSG00000144659), SLC25A26 (ENSG00000144741), SLC25A48 (ENSG00000145832), SLC25A37 (ENSG00000147454), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

Solute carrier family 25 member 44 — Q96H78 (reviewed: Q96H78)

All UniProt accessions (3): Q96H78, A0A804HJB0, E9PGQ0

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial solute transporter which transports branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria in brown adipose tissue (BAT). BAT is involved in BCAA catabolism and actively utilizes BCAA in the mitochondria for thermogenesis.

Subcellular location. Mitochondrion membrane.

Induction. Induction by cold exposure in brown adipose tissues.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family.

RefSeq proteins (8): NP_001273113, NP_001364314, NP_001364315, NP_001364316, NP_001364317, NP_001364318, NP_001364319, NP_055470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002067	MCP	Family
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR042164	SLC25A44	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 2 shown:

• L-valine(in) = L-valine(out) (RHEA:29703)
• L-leucine(in) = L-leucine(out) (RHEA:73011)

UniProt features (12 total): transmembrane region 6, repeat 3, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96H78-F1	80.66	0.36

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70895	Branched-chain amino acid catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 155 (showing top): ELVIDGE_HYPOXIA_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GENTILE_RESPONSE_CLUSTER_D3, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_ORGANIC_ACID_TRANSPORT, GGAANCGGAANY_UNKNOWN, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GENTILE_UV_HIGH_DOSE_DN, GOCC_MITOCHONDRIAL_ENVELOPE, chr1q22, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (5): amino acid transport (GO:0006865), branched-chain amino acid catabolic process (GO:0009083), branched-chain amino acid transport (GO:0015803), regulation of cold-induced thermogenesis (GO:0120161), transmembrane transport (GO:0055085)

GO Molecular Function (1): branched-chain amino acid transmembrane transporter activity (GO:0015658)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
amino acid catabolic process	1
branched-chain amino acid metabolic process	1
carboxylic acid catabolic process	1
carboxylic acid transport	1
nitrogen compound transport	1
regulation of multicellular organismal process	1
cold-induced thermogenesis	1
cellular process	1
branched-chain amino acid transport	1
carboxylic acid transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A44	A0A087WT04	A0A087WT04	696
SLC25A44	PMF1	Q6P1K2	677
SLC25A44	PPM1K	Q8N3J5	483
SLC25A44	ZNF442	Q9H7R0	480
SLC25A44	BCAT2	O15382	480
SLC25A44	SEMA4A	Q9H3S1	452
SLC25A44	ICA1L	Q8NDH6	447
SLC25A44	FAM117B	Q6P1L5	445
SLC25A44	MRPL47	Q9HD33	442
SLC25A44	BCKDHA	P12694	437
SLC25A44	NBEAL1	Q6ZS30	430
SLC25A44	TMEM150A	Q86TG1	424
SLC25A44	ZCCHC14	Q8WYQ9	417
SLC25A44	SLC25A51	Q9H1U9	417
SLC25A44	SEC14L6	B5MCN3	413

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SLC25A44	IMPDH2	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
SLC25A44	NME2P1	psi-mi:“MI:0914”(association)	0.350
SLC25A16	TOMM70	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): NME2P1 (Affinity Capture-MS), IMPDH2 (Affinity Capture-MS), LASP1 (Affinity Capture-MS), SLC25A44 (Affinity Capture-MS), IMPDH2 (Affinity Capture-MS), LASP1 (Affinity Capture-MS), SLC25A44 (Affinity Capture-RNA), IMPDH2 (Affinity Capture-MS), SLC25A44 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), SLC25A44 (Cross-Linking-MS (XL-MS)), SLC25A44 (Affinity Capture-MS), SLC25A44 (Affinity Capture-RNA), SLC25A44 (Co-fractionation)

ESM2 similar proteins: A1CIF6, A1CWA4, A2Q9F0, A3M019, A4RPU0, A5D9W9, A6RAY2, A6S8E0, A6ZXL1, A7F9Y3, A7TIQ0, B0DK57, B0Y4J4, B2MVX9, B2VSU4, B3LH09, O59674, P38087, P53320, Q01356, Q03829, Q07534, Q0CT66, Q12289, Q1DRJ3, Q2H608, Q2UU67, Q499U1, Q4PDL5, Q4WQC5, Q59KC4, Q5B717, Q5EAC0, Q5HZI9, Q5RD67, Q6BH02, Q6C6I3, Q6CNY8, Q6DE75, Q6DJ08

Diamond homologs: A1CIF6, A1CWA4, A2ASZ8, A2CEQ0, A2Q9F0, A3M019, A4RPU0, A5D9W9, A6RAY2, A6S8E0, A6ZXL1, A7F9Y3, A7TIQ0, B0DK57, B0Y4J4, B2MVX9, B2VSU4, B3LH09, G3XP90, O22261, O77792, O81845, P0CAT2, Q06143, Q07534, Q08CI8, Q0CT66, Q0II44, Q0V7M4, Q17QI7, Q1DRJ3, Q2H608, Q2UU67, Q499U1, Q4PDL5, Q4V8K4, Q4WQC5, Q54MZ4, Q54QI8, Q59KC4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

800 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156194244:GAAG:G	donor_gain	1.0000
1:156194247:GGT:G	donor_loss	1.0000
1:156194248:G:GG	donor_gain	1.0000
1:156194249:T:G	donor_loss	1.0000
1:156200470:CAGGT:C	donor_loss	0.9900
1:156200473:GTAA:G	donor_loss	0.9900
1:156200474:T:A	donor_loss	0.9900
1:156207876:T:TA	acceptor_gain	0.9900
1:156207884:A:AG	acceptor_gain	0.9900
1:156207885:G:GG	acceptor_gain	0.9900
1:156207934:A:AG	acceptor_gain	0.9900
1:156207935:A:G	acceptor_gain	0.9900
1:156207877:G:A	acceptor_gain	0.9800
1:156207885:GAGCA:G	acceptor_gain	0.9800
1:156200469:GCAG:G	donor_gain	0.9700
1:156210234:TTCCA:T	acceptor_loss	0.9700
1:156210235:TCCA:T	acceptor_loss	0.9700
1:156210236:CCA:C	acceptor_loss	0.9700
1:156210238:A:C	acceptor_loss	0.9700
1:156210239:G:GC	acceptor_loss	0.9700
1:156207885:GAGC:G	acceptor_gain	0.9600
1:156210239:GGTT:G	acceptor_gain	0.9600
1:156207885:GA:G	acceptor_gain	0.9500
1:156207909:A:AC	acceptor_gain	0.9400
1:156194246:AG:A	donor_gain	0.9300
1:156194247:GG:G	donor_gain	0.9300
1:156195035:A:AG	donor_gain	0.9300
1:156195718:G:GT	donor_gain	0.9300
1:156207881:TCCA:T	acceptor_loss	0.9300
1:156207883:CA:C	acceptor_loss	0.9300

AlphaMissense

2039 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156199883:G:C	W12C	1.000
1:156199883:G:T	W12C	1.000
1:156200440:C:A	A198D	1.000
1:156210386:G:C	K300N	1.000
1:156210386:G:T	K300N	1.000
1:156199881:T:A	W12R	0.999
1:156199881:T:C	W12R	0.999
1:156199891:T:C	L15P	0.999
1:156200074:G:A	G76E	0.999
1:156200140:G:C	R98P	0.999
1:156200191:C:A	A115D	0.999
1:156200194:G:A	G116D	0.999
1:156200196:G:C	G117R	0.999
1:156200197:G:A	G117D	0.999
1:156200203:C:A	A119D	0.999
1:156200220:A:C	S125R	0.999
1:156200222:C:A	S125R	0.999
1:156200222:C:G	S125R	0.999
1:156200233:C:A	P129H	0.999
1:156200400:G:C	G185R	0.999
1:156200448:T:A	W201R	0.999
1:156200448:T:C	W201R	0.999
1:156200450:G:C	W201C	0.999
1:156200450:G:T	W201C	0.999
1:156207955:C:A	A232D	0.999
1:156208006:G:C	R249P	0.999
1:156210315:G:C	G277R	0.999
1:156210369:G:C	G295R	0.999
1:156210393:A:C	S303R	0.999
1:156210395:C:A	S303R	0.999

dbSNP variants (sampled 300 via entrez): RS1000077425 (1:156192254 A>C), RS1000184287 (1:156212364 T>G), RS1000191825 (1:156207373 G>A), RS1000405143 (1:156199180 CAG>C), RS1000587568 (1:156197026 C>T), RS1000611464 (1:156212788 A>C), RS1000745999 (1:156204647 C>T), RS1000746396 (1:156198587 C>T), RS1000936920 (1:156197316 G>C), RS1001006903 (1:156199636 A>G), RS1001067983 (1:156212356 C>T), RS1001392289 (1:156205701 T>C), RS1001532647 (1:156205215 G>A), RS1001622727 (1:156197555 G>A,C,T), RS1001633017 (1:156212848 C>A,G,T)

Disease associations

OMIM: gene MIM:610824 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002022_1	Testicular germ cell tumor	3.000000e-08
GCST002389_1	Intracerebral hemorrhage	2.000000e-10
GCST004635_2	Testicular germ cell tumor	2.000000e-10
GCST004713_13	Testicular germ cell tumor	2.000000e-09
GCST005352_2	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-06

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 — Mitochondrial amino acid transporter subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Methotrexate	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1
Zinc	affects cotreatment, increases expression	1
Aflatoxin B1	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4CX	HCT116-SLC25A44-KO-c2	Cancer cell line	Male
CVCL_D4CY	HCT116-SLC25A44-KO-c6	Cancer cell line	Male
CVCL_TM51	HAP1 SLC25A44 (-) 1	Cancer cell line	Male
CVCL_XT07	HAP1 SLC25A44 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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