SARS2

Summary

SARS2 (seryl-tRNA synthetase 2, mitochondrial, HGNC:17697) is a protein-coding gene on chromosome 19q13.2, encoding Serine–tRNA ligase, mitochondrial (Q9NP81). Catalyzes the attachment of serine to tRNA(Ser). It is a selective cancer dependency (DepMap: 72.6% of cell lines).

This gene encodes the mitochondrial seryl-tRNA synthethase precursor, a member of the class II tRNA synthetase family. The mature enzyme catalyzes the ligation of Serine to tRNA(Ser) and participates in the biosynthesis of selenocysteinyl-tRNA(sec) in mitochondria. The enzyme contains an N-terminal tRNA binding domain and a core catalytic domain. It functions in a homodimeric form, which is stabilized by tRNA binding. This gene is regulated by a bidirectional promoter that also controls the expression of mitochondrial ribosomal protein S12. Both genes are within the critical interval for the autosomal dominant deafness locus DFNA4 and might be linked to this disease. Multiple transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 54938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 373 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 27
• Cancer dependency (DepMap): dependent in 72.6% of screened cell lines
• MANE Select transcript: NM_017827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17697
Approved symbol	SARS2
Name	seryl-tRNA synthetase 2, mitochondrial
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20450, mtSerRS, SerRSmt, SARS, SERS, SYS
Ensembl gene	ENSG00000104835
Ensembl biotype	protein_coding
OMIM	612804
Entrez	54938

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000221431, ENST00000430193, ENST00000455102, ENST00000593754, ENST00000594171, ENST00000594259, ENST00000597490, ENST00000598343, ENST00000598563, ENST00000598598, ENST00000598831, ENST00000600042, ENST00000600448, ENST00000602034, ENST00000897494, ENST00000897495, ENST00000915666, ENST00000961253, ENST00000961254, ENST00000961255

RefSeq mRNA: 2 — MANE Select: NM_017827 NM_001145901, NM_017827

CCDS: CCDS33017, CCDS54265

Canonical transcript exons

ENST00000221431 — 16 exons

Exon	Start	End
ENSE00000882557	38930470	38930763
ENSE00003207153	38917724	38917833
ENSE00003506602	38916221	38916314
ENSE00003563977	38916037	38916129
ENSE00003619123	38915841	38915906
ENSE00003632737	38915266	38915749
ENSE00004283206	38920086	38920149
ENSE00004283207	38918094	38918139
ENSE00004283208	38918766	38918813
ENSE00004283209	38919762	38919867
ENSE00004283210	38922238	38922267
ENSE00004283213	38918422	38918530
ENSE00004283214	38926205	38926300
ENSE00004283215	38921527	38921667
ENSE00004283216	38917921	38918008
ENSE00004283217	38921392	38921446

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 95.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9859 / max 166.7885, expressed in 1750 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180833	11.9859	1750

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.10	gold quality
right lobe of thyroid gland	UBERON:0001119	93.24	gold quality
metanephros cortex	UBERON:0010533	92.86	gold quality
right adrenal gland cortex	UBERON:0035827	92.61	gold quality
left lobe of thyroid gland	UBERON:0001120	92.53	gold quality
right adrenal gland	UBERON:0001233	92.43	gold quality
right lobe of liver	UBERON:0001114	92.10	gold quality
thyroid gland	UBERON:0002046	92.10	gold quality
lower esophagus mucosa	UBERON:0035834	91.92	gold quality
mucosa of transverse colon	UBERON:0004991	91.67	gold quality
left adrenal gland	UBERON:0001234	91.57	gold quality
left adrenal gland cortex	UBERON:0035825	91.36	gold quality
pituitary gland	UBERON:0000007	90.92	gold quality
cortex of kidney	UBERON:0001225	90.86	gold quality
primary visual cortex	UBERON:0002436	90.82	gold quality
right uterine tube	UBERON:0001302	90.63	gold quality
body of pancreas	UBERON:0001150	90.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.45	gold quality
adenohypophysis	UBERON:0002196	90.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.39	gold quality
esophagus mucosa	UBERON:0002469	90.37	gold quality
adrenal gland	UBERON:0002369	90.35	gold quality
right frontal lobe	UBERON:0002810	90.20	gold quality
prostate gland	UBERON:0002367	90.08	gold quality
minor salivary gland	UBERON:0001830	89.89	gold quality
body of stomach	UBERON:0001161	89.73	gold quality
saliva-secreting gland	UBERON:0001044	89.70	gold quality
cerebellar hemisphere	UBERON:0002245	89.66	gold quality
spleen	UBERON:0002106	89.65	gold quality
cerebellar cortex	UBERON:0002129	89.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4

miRNA regulators (miRDB)

14 targeting SARS2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-4513	95.04	67.06	727

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• NF-Y type CCAAT boxes are found preferentially in bidirectional Mrps12/Sarsm promoters, but many such promoters lack them and must be regulated in another way. (PMID:19439209)
• These data further support that the mitochondrial tRNA(Ser(UCN)) gene is the hot spot for mutations associated with hearing loss. (PMID:25968158)
• Phenotypic diversity of brain MRI patterns in mitochondrial aminoacyl-tRNA synthetase mutations. (PMID:33972171)
• The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4. (PMID:36056923)
• Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease. (PMID:36088542)
• Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease. (PMID:36350636)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sars2	ENSDARG00000102736
mus_musculus	Sars2	ENSMUSG00000070699
rattus_norvegicus	Sars2	ENSRNOG00000019962
drosophila_melanogaster	SerRS-m	FBGN0021750
caenorhabditis_elegans		WBGENE00005662

Paralogs (1): SARS1 (ENSG00000031698)

Protein

Protein identifiers

Serine–tRNA ligase, mitochondrial — Q9NP81 (reviewed: Q9NP81)

Alternative names: SerRSmt, Seryl-tRNA synthetase, Seryl-tRNA(Ser/Sec) synthetase

All UniProt accessions (7): Q9NP81, B4DJM9, M0QWZ7, M0QX29, M0R1C0, M0R259, M0R2H5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).

Subunit / interactions. Homodimer. The tRNA molecule probably binds across the dimer.

Subcellular location. Mitochondrion matrix.

Disease relevance. Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome (HUPRAS) [MIM:613845] A multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.

Pathway. Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP81-1	1	yes
Q9NP81-2	2

RefSeq proteins (2): NP_001139373, NP_060297* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002314	aa-tRNA-synt_IIb	Domain
IPR002317	Ser-tRNA-ligase_type_1	Family
IPR006195	aa-tRNA-synth_II	Domain
IPR010978	tRNA-bd_arm	Homologous_superfamily
IPR033729	SerRS_core	Domain
IPR042103	SerRS_1_N_sf	Homologous_superfamily
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily

Pfam: PF00587

Enzyme classification (BRENDA):

• EC 6.1.1.11 — serine-tRNA ligase (BRENDA: 32 organisms, 124 substrates, 45 inhibitors, 161 Km, 129 kcat entries)

Substrate kinetics (BRENDA)

35 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TRNASER	—	50
L-SERINE	0.0001–0.9	16
L-SER	0.0061–2.879	15
ATP	0.0001–0.49	12
SER	0.0003–0.45	6
TRNAUTUX	0.0012–0.0072	4
TRNASECUX	0.0037–0.0049	3
TRNASER-I-G-A	0.0008–0.0014	3
TRNASERGCU	0.35–0.37	3
TRNASERUGA	0.22–0.29	3
TRNAUTU1	0.0027–0.0057	3
D-SER	0.2	2
TRNASEC	0.0033–0.031	2
TRNASER(CGA)	0.0029–0.003	2
TRNASER(GCU)	0.0013–0.0053	2

Catalyzed reactions (Rhea), 2 shown:

• tRNA(Ser) + L-serine + ATP = L-seryl-tRNA(Ser) + AMP + diphosphate + H(+) (RHEA:12292)
• tRNA(Sec) + L-serine + ATP = L-seryl-tRNA(Sec) + AMP + diphosphate + H(+) (RHEA:42580)

UniProt features (57 total): strand 20, helix 16, turn 6, binding site 6, sequence variant 3, modified residue 2, transit peptide 1, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7YDF	X-RAY DIFFRACTION	2.8
7TZB	X-RAY DIFFRACTION	2.95
7YDG	X-RAY DIFFRACTION	3.2
8FFY	ELECTRON MICROSCOPY	3.6
7U2A	ELECTRON MICROSCOPY	4.1
7U2B	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP81-F1	90.58	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 299–301; 330–332; 345; 352; 418–421; 453

Post-translational modifications (2): 195, 110

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-379726	Mitochondrial tRNA aminoacylation
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 164 (showing top): GOBP_AMINO_ACID_ACTIVATION, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, REACTOME_MITOCHONDRIAL_TRNA_AMINOACYLATION, GOCC_MITOCHONDRIAL_MATRIX, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_TRNA_BINDING, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_OXYGEN_BONDS, GOMF_ADENYL_NUCLEOTIDE_BINDING, VERHAAK_GLIOBLASTOMA_CLASSICAL, BRUINS_UVC_RESPONSE_LATE, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP

GO Biological Process (4): seryl-tRNA aminoacylation (GO:0006434), mitochondrial seryl-tRNA aminoacylation (GO:0070158), translation (GO:0006412), tRNA aminoacylation for protein translation (GO:0006418)

GO Molecular Function (8): tRNA binding (GO:0000049), RNA binding (GO:0003723), serine-tRNA ligase activity (GO:0004828), ATP binding (GO:0005524), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
tRNA Aminoacylation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
conversion of seryl-tRNAsec to selenocys-tRNAsec	1
tRNA aminoacylation for protein translation	1
seryl-tRNA aminoacylation	1
tRNA aminoacylation for mitochondrial protein translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
tRNA aminoacylation	1
RNA binding	1
nucleic acid binding	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SARS2	PSTK	Q8IV42	990
SARS2	SEPSECS	Q9HD40	960
SARS2	RARS2	Q5T160	929
SARS2	LARS1	Q9P2J5	906
SARS2	RARS1	P54136	899
SARS2	LARS2	Q15031	899
SARS2	IARS2	Q9NSE4	881
SARS2	IARS1	P41252	873
SARS2	CARS1	P49589	857
SARS2	CARS2	Q9HA77	856
SARS2	YARS2	Q9Y2Z4	840
SARS2	AARS1	P49588	832
SARS2	TARS3	A2RTX5	812
SARS2	TARS2	Q9BW92	812
SARS2	YARS1	P54577	812

IntAct

62 interactions, top by confidence:

A	B	Type	Score
E7	RB1	psi-mi:“MI:0914”(association)	0.700
USP44	CETN2	psi-mi:“MI:0914”(association)	0.690
NTAQ1	SARS2	psi-mi:“MI:0915”(physical association)	0.560
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
FBXO17	NMT2	psi-mi:“MI:0914”(association)	0.530
KCMF1	IDH2	psi-mi:“MI:0914”(association)	0.530
USP15	PRPF3	psi-mi:“MI:0914”(association)	0.530
SARS2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
E7	COPE	psi-mi:“MI:0914”(association)	0.350
E7	RB1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CHCHD2	POLRMT	psi-mi:“MI:0914”(association)	0.350
CISD3	POLRMT	psi-mi:“MI:0914”(association)	0.350
PPTC7	BCKDHA	psi-mi:“MI:0914”(association)	0.350
SPATA20	PMPCB	psi-mi:“MI:0914”(association)	0.350
PPTC7	AKAP10	psi-mi:“MI:0914”(association)	0.350
SPATA20	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
DMWD	P4HA2	psi-mi:“MI:0914”(association)	0.350
	NUDT19	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
SQSTM1	CHEK1	psi-mi:“MI:0914”(association)	0.350
IGF1R	HAX1	psi-mi:“MI:0914”(association)	0.350
KEAP1	PTPRZ1	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): SARS2 (Reconstituted Complex), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), HARS2 (Co-fractionation), SARS2 (Co-fractionation), SBDS (Co-fractionation), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS), SARS2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A7SLX5, A7YY46, D3ZEY4, D3ZX08, E9QAM5, O59713, O95822, P0C7A1, P48760, P52333, P52824, Q002B5, Q07071, Q14397, Q15477, Q2KI24, Q2M296, Q2NKY8, Q3SYT1, Q3T7C9, Q3U1Y4, Q3URQ7, Q4R380, Q52L34, Q567W6, Q568Y2, Q5I0I8, Q5NCQ5, Q5ZHX9, Q6GPQ5, Q6NZR5, Q6P5E8, Q8BUI3, Q8BX80, Q8C9A2, Q8NFF5, Q8NFI3, Q91X44, Q920F5

Diamond homologs: A0AM81, A0JR71, A0LWR6, A0PX13, A0Q999, A0R638, A0RTS8, A1A0B7, A1KQG9, A1R120, A1SD34, A1TGX4, A1UN98, A1VYA9, A2BM70, A2SRC6, A3Q7P6, A5CNA2, A5U9G3, A6Q4S8, A7H4Y8, A7I890, A8FKH6, A9A4V3, A9BEX3, B0RCF1, B1L5G0, B1MEI9, B1VP80, B2HMM1, B2S3N6, B3DQG7, B5RL50, B5RR43, B5YEY8, B6YWW5, B7GN83, B7J1F4, B8DD73, B8DW52

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATF4	“up-regulates quantity by expression”	SARS2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrion organization	6	12.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	172
Likely benign	118
Benign	29

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
215111	NM_017827.4(SARS2):c.589+1G>A	Pathogenic
242874	NM_017827.4(SARS2):c.1042T>C (p.Phe348Leu)	Pathogenic
30982	NM_017827.4(SARS2):c.1169A>G (p.Asp390Gly)	Likely pathogenic
432215	NM_017827.4(SARS2):c.1413+1G>C	Likely pathogenic
638612	NM_017827.4(SARS2):c.1055A>C (p.Glu352Ala)	Likely pathogenic

SpliceAI

2489 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38916129:CCTGG:C	acceptor_loss	1.0000
19:38916130:C:CC	acceptor_gain	1.0000
19:38916130:C:CG	acceptor_loss	1.0000
19:38916131:T:A	acceptor_loss	1.0000
19:38916216:CTCA:C	donor_loss	1.0000
19:38916217:TCACC:T	donor_loss	1.0000
19:38916218:CA:C	donor_loss	1.0000
19:38916218:CAC:C	donor_loss	1.0000
19:38916219:A:AC	donor_gain	1.0000
19:38916219:A:AT	donor_loss	1.0000
19:38916220:C:CC	donor_gain	1.0000
19:38916220:C:G	donor_loss	1.0000
19:38916220:CCT:C	donor_gain	1.0000
19:38916220:CCTCT:C	donor_gain	1.0000
19:38916313:CC:C	acceptor_gain	1.0000
19:38916314:CC:C	acceptor_gain	1.0000
19:38916315:C:CC	acceptor_gain	1.0000
19:38916316:T:A	acceptor_loss	1.0000
19:38916319:G:T	acceptor_gain	1.0000
19:38916322:C:CT	acceptor_gain	1.0000
19:38916323:A:T	acceptor_gain	1.0000
19:38917697:C:A	donor_gain	1.0000
19:38917939:TCGA:T	donor_gain	1.0000
19:38918418:TCA:T	donor_loss	1.0000
19:38918419:CA:C	donor_loss	1.0000
19:38918420:A:AT	donor_loss	1.0000
19:38918421:CCT:C	donor_loss	1.0000
19:38918526:CCTTC:C	acceptor_loss	1.0000
19:38918527:CTTCC:C	acceptor_loss	1.0000
19:38918530:CCTGG:C	acceptor_loss	1.0000

AlphaMissense

3348 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38916121:A:C	S421R	0.997
19:38916121:A:T	S421R	0.997
19:38916123:T:G	S421R	0.997
19:38917927:G:C	F348L	0.996
19:38917927:G:T	F348L	0.996
19:38917929:A:G	F348L	0.996
19:38917993:G:C	S326R	0.996
19:38917993:G:T	S326R	0.996
19:38917995:T:G	S326R	0.996
19:38915900:C:G	A452P	0.995
19:38916094:G:C	S430R	0.995
19:38916094:G:T	S430R	0.995
19:38916096:T:G	S430R	0.995
19:38916270:C:G	R402P	0.995
19:38917987:G:C	C328W	0.994
19:38918808:G:C	F255L	0.994
19:38918808:G:T	F255L	0.994
19:38918810:A:G	F255L	0.994
19:38916109:G:C	C425W	0.992
19:38917921:C:A	K350N	0.992
19:38917921:C:G	K350N	0.992
19:38915893:G:T	A454D	0.991
19:38917826:A:C	M353R	0.991
19:38917986:A:C	Y329D	0.991
19:38916117:A:G	S423P	0.990
19:38916116:G:A	S423F	0.988
19:38916122:C:A	S421I	0.988
19:38916122:C:T	S421N	0.988
19:38916100:G:C	F428L	0.987
19:38916100:G:T	F428L	0.987

dbSNP variants (sampled 300 via entrez): RS1000341133 (19:38927477 T>C), RS1000407808 (19:38923660 C>A,T), RS1000919376 (19:38923561 G>A), RS1001865117 (19:38923146 C>A,G), RS1001935298 (19:38918085 A>G), RS1002009526 (19:38928288 C>G,T), RS1002190411 (19:38924535 G>A,T), RS1002197644 (19:38928887 A>T), RS1002300430 (19:38929989 T>C), RS1002436163 (19:38929777 C>A,G,T), RS1002505771 (19:38932616 G>C), RS1002637535 (19:38931034 G>A,T), RS1002734167 (19:38924249 C>T), RS1003267916 (19:38916554 T>C), RS1003345807 (19:38917107 T>C)

Disease associations

OMIM: gene MIM:612804 | disease phenotypes: MIM:613845

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (1): hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (MONDO:0013458)

Orphanet (1): Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (Orphanet:363694)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000103	Polyuria
HP:0000127	Renal salt wasting
HP:0000819	Diabetes mellitus
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001622	Premature birth
HP:0001873	Thrombocytopenia
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001903	Anemia
HP:0002092	Pulmonary arterial hypertension
HP:0002093	Respiratory insufficiency
HP:0002149	Hyperuricemia
HP:0002151	Increased circulating lactate concentration
HP:0002878	Respiratory failure
HP:0002902	Hyponatremia
HP:0002917	Hypomagnesemia
HP:0003138	Increased blood urea nitrogen
HP:0003554	Type 2 muscle fiber atrophy
HP:0003593	Infantile onset
HP:0004719	Hyperechogenic kidneys
HP:0005977	Hypochloremic metabolic alkalosis
HP:0011968	Feeding difficulties
HP:0012622	Chronic kidney disease

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

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, affects expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, affects expression	2
dicrotophos	increases expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	increases abundance, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Dactinomycin	increases secretion, affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects cotreatment	1
Potassium Dichromate	increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

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