SDS

Summary

SDS (serine dehydratase, HGNC:10691) is a protein-coding gene on chromosome 12q24.13, encoding L-serine dehydratase/L-threonine deaminase (P20132). Catalyzes the pyridoxal-phosphate-dependent dehydrative deamination of L-threonine and L-serine to ammonia and alpha-ketobutyrate and pyruvate, respectively.

This gene encodes one of three enzymes that are involved in metabolizing serine and glycine. L-serine dehydratase converts L-serine to pyruvate and ammonia and requires pyridoxal phosphate as a cofactor. The encoded protein can also metabolize threonine to NH4+ and 2-ketobutyrate. The encoded protein is found predominantly in the liver.

Source: NCBI Gene 10993 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_006843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10691
Approved symbol	SDS
Name	serine dehydratase
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	SDH
Ensembl gene	ENSG00000135094
Ensembl biotype	protein_coding
OMIM	182128
Entrez	10993

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 24 protein_coding, 3 retained_intron

ENST00000257549, ENST00000546639, ENST00000546785, ENST00000547342, ENST00000552280, ENST00000553112, ENST00000880846, ENST00000880847, ENST00000880848, ENST00000880849, ENST00000880850, ENST00000880851, ENST00000880852, ENST00000880853, ENST00000880854, ENST00000880855, ENST00000880856, ENST00000880857, ENST00000880858, ENST00000880859, ENST00000880860, ENST00000880861, ENST00000880862, ENST00000880863, ENST00000880864, ENST00000880865, ENST00000880866

RefSeq mRNA: 1 — MANE Select: NM_006843 NM_006843

CCDS: CCDS9169

Canonical transcript exons

ENST00000257549 — 8 exons

Exon	Start	End
ENSE00000918009	113392445	113393149
ENSE00000918010	113393892	113394016
ENSE00000918011	113397165	113397392
ENSE00002245314	113403768	113403887
ENSE00003466531	113399112	113399151
ENSE00003510987	113399556	113399710
ENSE00003527497	113398707	113398846
ENSE00003786782	113398515	113398606

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 11.1335 / max 1538.1238, expressed in 291 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133361	10.8476	288
133362	0.2545	107
133360	0.0314	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.87	gold quality
liver	UBERON:0002107	96.31	gold quality
putamen	UBERON:0001874	89.71	gold quality
caudate nucleus	UBERON:0001873	88.59	gold quality
secondary oocyte	CL:0000655	86.38	gold quality
oocyte	CL:0000023	86.36	gold quality
nucleus accumbens	UBERON:0001882	85.60	gold quality
amygdala	UBERON:0001876	81.06	gold quality
substantia nigra	UBERON:0002038	80.89	gold quality
hypothalamus	UBERON:0001898	79.44	gold quality
midbrain	UBERON:0001891	78.88	gold quality
right frontal lobe	UBERON:0002810	78.20	gold quality
left adrenal gland cortex	UBERON:0035825	78.03	gold quality
buccal mucosa cell	CL:0002336	78.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.24	gold quality
right adrenal gland cortex	UBERON:0035827	77.19	gold quality
cingulate cortex	UBERON:0003027	76.73	gold quality
adrenal cortex	UBERON:0001235	76.64	gold quality
anterior cingulate cortex	UBERON:0009835	76.58	gold quality
telencephalon	UBERON:0001893	75.93	gold quality
left adrenal gland	UBERON:0001234	75.75	gold quality
islet of Langerhans	UBERON:0000006	74.75	gold quality
temporal lobe	UBERON:0001871	74.71	gold quality
tendon of biceps brachii	UBERON:0008188	74.53	gold quality
forebrain	UBERON:0001890	74.37	gold quality
Ammon’s horn	UBERON:0001954	74.28	gold quality
gall bladder	UBERON:0002110	74.20	gold quality
medial globus pallidus	UBERON:0002477	73.93	silver quality
endometrium epithelium	UBERON:0004811	73.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.80
E-MTAB-5061	no	3.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

10 targeting SDS, 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-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Literature-anchored findings (GeneRIF, showing 2)

• S84A serine racemase mutant behaved like serine dehydratase, whereas A65S serine dehydratase mutant acquired an additional function of using D-serine as a substrate. (PMID:23112234)
• SDS expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sds	ENSMUSG00000029597
rattus_norvegicus	Sds	ENSRNOG00000001388
caenorhabditis_elegans		WBGENE00007653
caenorhabditis_elegans		WBGENE00008490
caenorhabditis_elegans		WBGENE00008732
caenorhabditis_elegans		WBGENE00010759
caenorhabditis_elegans		WBGENE00019094
caenorhabditis_elegans		WBGENE00019096
caenorhabditis_elegans		WBGENE00019962

Paralogs (5): SDSL (ENSG00000139410), THNSL2 (ENSG00000144115), CBS (ENSG00000160200), SRR (ENSG00000167720), THNSL1 (ENSG00000185875)

Protein

Protein identifiers

L-serine dehydratase/L-threonine deaminase — P20132 (reviewed: P20132)

Alternative names: Hepatic serine dehydratase, L-serine deaminase, L-threonine dehydratase

All UniProt accessions (3): P20132, F8VW93, F8VXS0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the pyridoxal-phosphate-dependent dehydrative deamination of L-threonine and L-serine to ammonia and alpha-ketobutyrate and pyruvate, respectively.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in the perivenous regions of the liver.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Similarity. Belongs to the serine/threonine dehydratase family.

RefSeq proteins (1): NP_006834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000634	Ser/Thr_deHydtase_PyrdxlP-BS	Binding_site
IPR001926	TrpB-like_PALP	Domain
IPR036052	TrpB-like_PALP_sf	Homologous_superfamily
IPR050147	Ser/Thr_Dehydratase	Family

Pfam: PF00291

Enzyme classification (BRENDA):

• EC 4.3.1.17 — L-serine ammonia-lyase (BRENDA: 34 organisms, 69 substrates, 60 inhibitors, 97 Km, 57 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-SERINE	0.0026–189	51
L-SER	0.8–420	16
D-SERINE	3.2–75	7
SERINE	30.7–67.3	6
THREONINE	3.1–59.5	6
L-THREONINE	0.5–57	4
D-THREONINE	55–60	2
L-SERINE O-SULFATE	0.49	1
L-THR	130	1
BETA-CHLORO-L-ALANINE	—	0
L-THREO-3-HYDROXYASPARTATE	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-serine = pyruvate + NH4(+) (RHEA:19169)
• L-threonine = 2-oxobutanoate + NH4(+) (RHEA:22108)

UniProt features (38 total): helix 17, strand 11, sequence conflict 5, mutagenesis site 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4H27	X-RAY DIFFRACTION	1.3
1P5J	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20132-F1	95.77	0.93

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 (1): 128

Post-translational modifications (1): 41

Mutagenesis-validated functional residues (2):

Position	Phenotype
128	reduced km and vmax for both l-serine and l-threonine. 10-fold increase in dissociation constant for pyridoxal-phosphate
303	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8849175	Threonine catabolism
R-HSA-977347	Serine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 145 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GNF2_GSTM1, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GNF2_HPN, MODULE_528, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN

GO Biological Process (6): gluconeogenesis (GO:0006094), L-serine catabolic process (GO:0006565), lipid metabolic process (GO:0006629), pyruvate biosynthetic process (GO:0042866), amino acid metabolic process (GO:0006520), small molecule biosynthetic process (GO:0044283)

GO Molecular Function (6): L-serine ammonia-lyase activity (GO:0003941), threonine deaminase activity (GO:0004794), pyridoxal phosphate binding (GO:0030170), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (3): mitochondrion (GO:0005739), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	2
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
ammonia-lyase activity	2
cytoplasm	2
cellular anatomical structure	2
glucose metabolic process	1
hexose biosynthetic process	1
L-serine metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
pyruvate metabolic process	1
monocarboxylic acid biosynthetic process	1
biosynthetic process	1
small molecule metabolic process	1
anion binding	1
vitamin B6 binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDS	TAT	P17735	725
SDS	PLOD2	O00469	697
SDS	OAT	P04181	617
SDS	PSPH	P78330	531
SDS	HAL	P42357	526
SDS	AGXT	P21549	508
SDS	SHMT2	P34897	497
SDS	AASS	Q9UDR5	493
SDS	PC	P11498	490
SDS	SHMT1	P34896	487
SDS	AMT	P48728	486
SDS	ASS1	P00966	469
SDS	CTH	P32929	469
SDS	GLUL	P15104	464
SDS	HGD	Q93099	462

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SDS	DDI1	psi-mi:“MI:0915”(physical association)	0.560
SDS	TGM7	psi-mi:“MI:0915”(physical association)	0.560
HGS	SDS	psi-mi:“MI:0915”(physical association)	0.560
SDS	FADD	psi-mi:“MI:0915”(physical association)	0.400
SDS	DDI1	psi-mi:“MI:0915”(physical association)	0.000
HGS	SDS	psi-mi:“MI:0915”(physical association)	0.000
TGM7	SDS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): TGM7 (Two-hybrid), DDI1 (Two-hybrid), HGS (Two-hybrid), FADD (Affinity Capture-MS)

ESM2 similar proteins: A0A6N3IN21, A3KCL7, A4IFH5, A7MBC0, A7MBI7, D3ZDK7, D3ZDM7, E1BNQ4, P09367, P10950, P11172, P13439, P17256, P20132, P24298, P25409, P31754, P46597, P50053, P97328, Q02974, Q03426, Q0VCW4, Q1JPD3, Q3B8E3, Q3TY86, Q3ZKN0, Q5BJJ5, Q5E9T8, Q5M7T9, Q5R514, Q5R824, Q5RD71, Q5RFE6, Q6PCB7, Q6SKR2, Q80W22, Q8CHP8, Q8CIM3, Q8HZJ0

Diamond homologs: A0A6N3IN21, A0FKE6, A6ZVB1, B3LU13, B5VKE8, C8ZAU6, P00927, P04968, P09367, P0CF21, P0CF22, P0CF23, P20132, P20506, P25379, P37946, P46493, P53607, P55664, P66898, P9WG94, P9WG95, Q0VCW4, Q74FW6, Q86B06, Q8R238, Q8VBT2, Q96GA7, Q9CKJ2, Q9WYJ1, Q9X7F1, Q9ZSS6, A0R220, A1B8Z2, A2XWA9, A4F2N8, O28672, O42615, O57809, O59791

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1137 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113393846:AGCG:A	donor_gain	1.0000
12:113393895:CGAA:C	donor_gain	1.0000
12:113394035:C:T	acceptor_gain	1.0000
12:113397159:GCTCA:G	donor_loss	1.0000
12:113397160:CTCAC:C	donor_loss	1.0000
12:113397161:TCACC:T	donor_loss	1.0000
12:113397162:CAC:C	donor_loss	1.0000
12:113397163:ACC:A	donor_loss	1.0000
12:113397164:C:CG	donor_loss	1.0000
12:113397388:CTTCC:C	acceptor_gain	1.0000
12:113397391:CC:C	acceptor_gain	1.0000
12:113397392:CC:C	acceptor_gain	1.0000
12:113398510:CATA:C	donor_loss	1.0000
12:113398511:ATACC:A	donor_loss	1.0000
12:113398513:A:AC	donor_gain	1.0000
12:113398513:ACCAG:A	donor_loss	1.0000
12:113398514:C:CA	donor_loss	1.0000
12:113398514:C:CC	donor_gain	1.0000
12:113398602:AATAA:A	acceptor_gain	1.0000
12:113398603:ATAA:A	acceptor_gain	1.0000
12:113398604:TAA:T	acceptor_gain	1.0000
12:113398606:AC:A	acceptor_loss	1.0000
12:113398607:C:CC	acceptor_gain	1.0000
12:113398608:T:G	acceptor_loss	1.0000
12:113398616:C:CT	acceptor_gain	1.0000
12:113398616:C:T	acceptor_gain	1.0000
12:113398703:TCAC:T	donor_loss	1.0000
12:113398704:CACCT:C	donor_loss	1.0000
12:113398705:ACCTC:A	donor_loss	1.0000
12:113398706:C:CT	donor_loss	1.0000

AlphaMissense

2124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113399589:G:C	F40L	0.989
12:113399589:G:T	F40L	0.989
12:113399591:A:G	F40L	0.989
12:113397249:A:T	V190D	0.988
12:113399619:C:A	K30N	0.987
12:113399619:C:G	K30N	0.987
12:113399586:C:A	K41N	0.986
12:113399586:C:G	K41N	0.986
12:113393919:C:G	A251P	0.983
12:113398532:A:C	F136L	0.982
12:113398532:A:T	F136L	0.982
12:113398534:A:G	F136L	0.982
12:113393117:C:A	G271W	0.981
12:113393118:G:C	C270W	0.981
12:113397243:G:T	A192D	0.981
12:113394016:A:C	S218R	0.980
12:113394016:A:T	S218R	0.980
12:113397166:T:G	S218R	0.980
12:113397237:T:A	E194V	0.980
12:113397279:A:G	L180P	0.979
12:113397363:A:G	L152P	0.978
12:113398839:G:C	N67K	0.978
12:113398839:G:T	N67K	0.978
12:113399629:A:T	V27D	0.978
12:113397330:A:T	I163N	0.977
12:113398813:G:T	A76D	0.977
12:113399123:A:T	V61D	0.977
12:113393116:C:T	G271E	0.976
12:113397265:A:G	W185R	0.976
12:113397265:A:T	W185R	0.976

dbSNP variants (sampled 300 via entrez): RS1000213283 (12:113403972 C>T), RS1000263857 (12:113404158 C>A,T), RS1000541369 (12:113399440 G>A,T), RS1000914192 (12:113404252 T>C,G), RS1001137862 (12:113393201 C>T), RS1001141376 (12:113400608 C>T), RS1001303375 (12:113405020 T>G), RS1001515865 (12:113392330 G>A), RS1001577983 (12:113392679 G>A,C,T), RS1001881583 (12:113402887 G>A), RS1001933727 (12:113403180 G>A), RS1002172348 (12:113403417 G>A,T), RS1002319970 (12:113398245 A>G), RS1002550524 (12:113400656 AT>A), RS1002658047 (12:113392843 G>A,C)

Disease associations

OMIM: gene MIM:182128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003391_9	Low high density lipoprotein cholesterol levels	8.000000e-06
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
aristolochic acid I	increases expression	1
bismuth tripotassium dicitrate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
ortho-topolin riboside	affects cotreatment, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Aspirin	increases expression	1
Benzene	increases expression	1
Calcitriol	decreases expression	1
Endosulfan	increases expression, decreases expression, decreases reaction	1
Melatonin	affects cotreatment, decreases expression	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Theophylline	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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