SDSL

Summary

SDSL (serine dehydratase like, HGNC:30404) is a protein-coding gene on chromosome 12q24.13, encoding Serine dehydratase-like (Q96GA7). Catalyzes the pyridoxal-phosphate-dependent dehydrative deamination of L-threonine and L-serine to ammonia and alpha-ketobutyrate and pyruvate, respectively.

Enables L-serine ammonia-lyase activity; identical protein binding activity; and threonine deaminase activity. Predicted to be involved in L-serine catabolic process. Predicted to be located in cytosol.

Source: NCBI Gene 113675 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001304993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30404
Approved symbol	SDSL
Name	serine dehydratase like
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	SDS-RS1, cSDH
Ensembl gene	ENSG00000139410
Ensembl biotype	protein_coding
OMIM	620735
Entrez	113675

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 31 protein_coding

ENST00000345635, ENST00000403593, ENST00000546672, ENST00000547802, ENST00000551760, ENST00000553248, ENST00000874044, ENST00000874045, ENST00000874046, ENST00000874047, ENST00000874048, ENST00000874049, ENST00000874050, ENST00000874051, ENST00000874052, ENST00000874053, ENST00000874054, ENST00000874055, ENST00000874056, ENST00000874057, ENST00000874058, ENST00000874059, ENST00000874060, ENST00000874061, ENST00000874062, ENST00000874063, ENST00000874064, ENST00000964525, ENST00000964526, ENST00000964527, ENST00000964528

RefSeq mRNA: 2 — MANE Select: NM_001304993 NM_001304993, NM_138432

CCDS: CCDS9170

Canonical transcript exons

ENST00000403593 — 8 exons

Exon	Start	End
ENSE00000938004	113429160	113429299
ENSE00000938005	113434134	113434222
ENSE00000998190	113435329	113435556
ENSE00000998193	113436751	113436875
ENSE00001128196	113437886	113438276
ENSE00001392322	113427962	113428156
ENSE00002342298	113422380	113422477
ENSE00003759641	113428420	113428459

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 95.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9077 / max 215.6569, expressed in 1624 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128196	7.4358	1618
128195	0.4719	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.07	gold quality
mucosa of transverse colon	UBERON:0004991	91.66	gold quality
right adrenal gland	UBERON:0001233	90.99	gold quality
liver	UBERON:0002107	90.23	gold quality
right adrenal gland cortex	UBERON:0035827	90.23	gold quality
right lobe of thyroid gland	UBERON:0001119	89.95	gold quality
kidney epithelium	UBERON:0004819	89.70	gold quality
left adrenal gland	UBERON:0001234	89.37	gold quality
adult mammalian kidney	UBERON:0000082	89.06	gold quality
left adrenal gland cortex	UBERON:0035825	88.76	gold quality
left lobe of thyroid gland	UBERON:0001120	88.23	gold quality
adrenal cortex	UBERON:0001235	87.77	gold quality
thyroid gland	UBERON:0002046	87.71	gold quality
adrenal gland	UBERON:0002369	87.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.00	gold quality
adenohypophysis	UBERON:0002196	84.70	gold quality
spinal cord	UBERON:0002240	84.31	gold quality
apex of heart	UBERON:0002098	84.21	gold quality
kidney	UBERON:0002113	83.76	gold quality
body of pancreas	UBERON:0001150	83.64	gold quality
pituitary gland	UBERON:0000007	83.37	gold quality
pancreas	UBERON:0001264	81.74	gold quality
substantia nigra	UBERON:0002038	81.37	gold quality
metanephros cortex	UBERON:0010533	81.03	gold quality
hypothalamus	UBERON:0001898	80.95	gold quality
metanephros	UBERON:0000081	80.89	gold quality
heart left ventricle	UBERON:0002084	79.96	gold quality
duodenum	UBERON:0002114	79.95	gold quality
transverse colon	UBERON:0001157	79.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	7.29
E-MTAB-6142	no	42.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting SDSL, 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-5193	100.00	67.26	1744
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4743-5P	88.08	64.31	91

Literature-anchored findings (GeneRIF, showing 1)

• The crystal structure of SDSL has been determined. Site-directed mutagenesis studies suggest that having a glycine at residue 72 of SDSL is the major reason for the reduction of its catalytic activity, in comparison with the liver enzyme (SDS). (PMID:18342636)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdsl	ENSDARG00000074698
mus_musculus	Sdsl	ENSMUSG00000029596
rattus_norvegicus	Sdsl	ENSRNOG00000001391
caenorhabditis_elegans		WBGENE00007653
caenorhabditis_elegans		WBGENE00008490
caenorhabditis_elegans		WBGENE00008732
caenorhabditis_elegans		WBGENE00010759
caenorhabditis_elegans		WBGENE00019094
caenorhabditis_elegans		WBGENE00019096
caenorhabditis_elegans		WBGENE00019962

Paralogs (5): SDS (ENSG00000135094), THNSL2 (ENSG00000144115), CBS (ENSG00000160200), SRR (ENSG00000167720), THNSL1 (ENSG00000185875)

Protein

Protein identifiers

Serine dehydratase-like — Q96GA7 (reviewed: Q96GA7)

Alternative names: Cancerous serine dehydratase, Glutamate racemase, L-serine deaminase, L-serine dehydratase/L-threonine deaminase, L-threonine dehydratase, Serine dehydratase 2

All UniProt accessions (5): Q96GA7, F8VYZ3, F8VZ97, H0YIA2, H0YID3

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. Also exhibits racemase activity towards L-glutamate and D-glutamate.

Subunit / interactions. Monomer. Homodimer.

Tissue specificity. Expressed in lung cancer cell lines.

Similarity. Belongs to the serine/threonine dehydratase family.

RefSeq proteins (2): NP_001291922, NP_612441 (=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), 3 shown:

• L-glutamate = D-glutamate (RHEA:12813)
• L-serine = pyruvate + NH4(+) (RHEA:19169)
• L-threonine = 2-oxobutanoate + NH4(+) (RHEA:22108)

UniProt features (33 total): helix 15, strand 12, mutagenesis site 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2RKB	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GA7-F1	95.22	0.91

Functional residue map

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

Post-translational modifications (2): 1, 48

Mutagenesis-validated functional residues (3):

Position	Phenotype
72	strongly increased enzyme activity towards threonine.
287	almost no change in km and vmax for serine and threonine. significantly increased protein levels.
309	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: 100 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_AMINO_ACID_CATABOLIC_PROCESS, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP, GOMF_RACEMASE_AND_EPIMERASE_ACTIVITY, chr12q24, GOMF_VITAMIN_BINDING, GOMF_ISOMERASE_ACTIVITY, GOBP_L_SERINE_METABOLIC_PROCESS, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA

GO Biological Process (3): L-serine catabolic process (GO:0006565), lipid metabolic process (GO:0006629), amino acid metabolic process (GO:0006520)

GO Molecular Function (7): L-serine ammonia-lyase activity (GO:0003941), threonine deaminase activity (GO:0004794), glutamate racemase activity (GO:0008881), pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), lyase activity (GO:0016829), isomerase activity (GO:0016853)

GO Cellular Component (1): cytosol (GO:0005829)

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
catalytic activity	2
L-serine metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
amino-acid racemase activity	1
anion binding	1
vitamin B6 binding	1
protein binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDSL	PLOD2	O00469	765
SDSL	AMT	P48728	537
SDSL	CERS4	Q9HA82	474
SDSL	GLDC	P23378	450
SDSL	CCDC74A	Q96AQ1	437
SDSL	HACD4	Q5VWC8	435
SDSL	GCAT	O75600	421
SDSL	ERCC6L	Q2NKX8	414
SDSL	HGD	Q93099	410
SDSL	AGXT	P21549	410
SDSL	CS	O75390	393
SDSL	MCEE	Q96PE7	388
SDSL	REEP6	Q96HR9	387
SDSL	COASY	Q13057	383
SDSL	HACD3	Q9P035	380

IntAct

12 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
SDSL	SDSL	psi-mi:“MI:0915”(physical association)	0.800
TUBGCP4	SDSL	psi-mi:“MI:0915”(physical association)	0.490
TUBGCP4	SDSL	psi-mi:“MI:0915”(physical association)	0.370
RAMP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
SDSL	SDSL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): SDSL (Two-hybrid), SDSL (Two-hybrid), SDSL (Two-hybrid), SDSL (Two-hybrid), SDSL (Two-hybrid), SDSL (Co-fractionation), SDSL (Co-fractionation), SDSL (Affinity Capture-MS), SDSL (Affinity Capture-MS), SDSL (Affinity Capture-RNA), SDSL (Proximity Label-MS), SDSL (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

965 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113422405:A:T	donor_gain	1.0000
12:113427961:G:GA	acceptor_loss	1.0000
12:113427961:GGCT:G	acceptor_gain	1.0000
12:113428093:GT:G	donor_gain	1.0000
12:113428154:G:GT	donor_gain	1.0000
12:113429153:T:TA	acceptor_gain	1.0000
12:113429155:CACAG:C	acceptor_loss	1.0000
12:113429156:A:AG	acceptor_gain	1.0000
12:113429156:ACAG:A	acceptor_gain	1.0000
12:113429156:ACAGG:A	acceptor_gain	1.0000
12:113429157:CA:C	acceptor_loss	1.0000
12:113429158:AG:A	acceptor_gain	1.0000
12:113429158:AGGG:A	acceptor_gain	1.0000
12:113429159:GG:G	acceptor_gain	1.0000
12:113429159:GGGG:G	acceptor_gain	1.0000
12:113429297:AAGGT:A	donor_loss	1.0000
12:113429298:AGGTA:A	donor_loss	1.0000
12:113429299:GGT:G	donor_loss	1.0000
12:113429300:G:A	donor_loss	1.0000
12:113429301:T:A	donor_loss	1.0000
12:113436736:T:TA	acceptor_gain	1.0000
12:113436749:A:AG	acceptor_gain	1.0000
12:113436750:G:GT	acceptor_gain	1.0000
12:113436872:CTGGG:C	donor_loss	1.0000
12:113436874:GG:G	donor_gain	1.0000
12:113436874:GGGT:G	donor_loss	1.0000
12:113436875:GG:G	donor_gain	1.0000
12:113436875:GGTG:G	donor_loss	1.0000
12:113436876:G:GG	donor_gain	1.0000
12:113436877:T:G	donor_loss	1.0000

AlphaMissense

2112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113434203:T:C	F142L	0.996
12:113434205:T:A	F142L	0.996
12:113434205:T:G	F142L	0.996
12:113428126:G:C	K48N	0.994
12:113428126:G:T	K48N	0.994
12:113428121:T:C	F47L	0.993
12:113428123:C:A	F47L	0.993
12:113428123:C:G	F47L	0.993
12:113429167:T:A	N74K	0.989
12:113429167:T:G	N74K	0.989
12:113429178:C:A	A78D	0.988
12:113428098:A:T	E39V	0.987
12:113436839:G:C	D254H	0.987
12:113428124:A:G	K48E	0.986
12:113435426:G:T	G181W	0.986
12:113434195:T:A	V139D	0.985
12:113435555:A:C	S224R	0.985
12:113436751:T:A	S224R	0.985
12:113436751:T:G	S224R	0.985
12:113436756:C:A	A226D	0.985
12:113428148:T:C	C56R	0.984
12:113429172:G:A	G76D	0.984
12:113437918:G:T	G277W	0.983
12:113434158:G:C	A127P	0.982
12:113428093:G:C	K37N	0.981
12:113428093:G:T	K37N	0.981
12:113428125:A:C	K48T	0.981
12:113428450:T:C	C69R	0.981
12:113429184:C:A	A80D	0.981
12:113429193:C:A	A83D	0.981

dbSNP variants (sampled 300 via entrez): RS1000047804 (12:113434078 G>A), RS1000071921 (12:113431862 C>G), RS1000078800 (12:113433795 G>A,T), RS1000181880 (12:113427391 G>A,T), RS1000383268 (12:113421789 C>T), RS1000425035 (12:113432199 T>G), RS1000476675 (12:113421944 T>C), RS1000537715 (12:113427604 C>A,T), RS1000725524 (12:113427669 G>A), RS1001030570 (12:113433520 G>A), RS1001050855 (12:113432648 T>C), RS1001082005 (12:113432406 A>G), RS1001152431 (12:113425500 AG>A), RS1001204593 (12:113425237 T>C), RS1001533795 (12:113433038 G>A)

Disease associations

OMIM: gene MIM:620735 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	4
Benzo(a)pyrene	decreases expression, increases methylation	3
sodium arsenite	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
aristolochic acid I	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
bisphenol A	increases expression	1
aflatoxin B2	increases methylation	1
resorcinol	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Gallic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	affects expression	1

Clinical trials (associated diseases)

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