ACCSL

Summary

ACCSL (1-aminocyclopropane-1-carboxylate synthase homolog (inactive) like, HGNC:34391) is a protein-coding gene on chromosome 11p11.2, encoding Probable inactive 1-aminocyclopropane-1-carboxylate synthase-like protein 2 (Q4AC99).

Predicted to enable transaminase activity. Predicted to be involved in amino acid metabolic process.

Source: NCBI Gene 390110 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total — 1 pathogenic
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_001031854
• Notable: 91 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34391
Approved symbol	ACCSL
Name	1-aminocyclopropane-1-carboxylate synthase homolog (inactive) like
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205126
Ensembl biotype	protein_coding
Entrez	390110

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000378832

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

ENST00000378832, ENST00000527145

RefSeq mRNA: 2 — MANE Select: NM_001031854 NM_001031854, NM_001363113

CCDS: CCDS41636

Canonical transcript exons

ENST00000378832 — 14 exons

Exon	Start	End
ENSE00001478892	44059838	44059977
ENSE00001478914	44050062	44050121
ENSE00001478916	44047981	44048540
ENSE00003489752	44052991	44053068
ENSE00003493368	44058546	44058699
ENSE00003494818	44053406	44053506
ENSE00003507044	44052662	44052759
ENSE00003510117	44055202	44055291
ENSE00003595394	44051653	44051719
ENSE00003620025	44056040	44056085
ENSE00003645274	44056185	44056326
ENSE00003658545	44050552	44050622
ENSE00003661166	44058317	44058459
ENSE00003665395	44051335	44051404

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 83.76.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, monocyte, leukocyte, sural nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACCSL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	1.6e-10	+2.15	11:43919901:T:C
Brain Cerebellar Hemisphere	eqtl	1.2e-07	+1.81	11:43919901:T:C
Ovary	eqtl	3.3e-02	+1.54	11:43919901:T:C
Artery Tibial	eqtl	4.2e-02	+0.89	11:43899605:C:T

Top tissues by expression

showing 100 of 107 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.10	silver quality
monocyte	CL:0000576	56.76	gold quality
leukocyte	CL:0000738	56.01	gold quality
sural nerve	UBERON:0015488	41.33	gold quality
stromal cell of endometrium	CL:0002255	39.29	gold quality
bone marrow cell	CL:0002092	38.55	gold quality
granulocyte	CL:0000094	37.42	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skin of leg	UBERON:0001511	37.15	silver quality
zone of skin	UBERON:0000014	36.53	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of stomach	UBERON:0001199	36.25	silver quality
bone marrow	UBERON:0002371	35.52	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right coronary artery	UBERON:0001625	34.99	gold quality
descending thoracic aorta	UBERON:0002345	34.79	gold quality
placenta	UBERON:0001987	34.70	gold quality
testis	UBERON:0000473	34.42	gold quality
ectocervix	UBERON:0012249	34.42	silver quality
right testis	UBERON:0004534	34.37	silver quality
right uterine tube	UBERON:0001302	34.10	gold quality
left testis	UBERON:0004533	33.96	silver quality
smooth muscle tissue	UBERON:0001135	33.46	gold quality
muscle tissue	UBERON:0002385	33.43	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
cerebellar cortex	UBERON:0002129	32.27	gold quality
cerebellum	UBERON:0002037	32.24	gold quality
left uterine tube	UBERON:0001303	32.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
cerebellar hemisphere	UBERON:0002245	32.09	gold quality
gall bladder	UBERON:0002110	31.91	silver quality
right hemisphere of cerebellum	UBERON:0014890	31.47	gold quality
tonsil	UBERON:0002372	31.38	silver quality
prefrontal cortex	UBERON:0000451	31.13	gold quality
liver	UBERON:0002107	31.07	gold quality
myometrium	UBERON:0001296	30.66	gold quality
thoracic aorta	UBERON:0001515	30.65	gold quality
left coronary artery	UBERON:0001626	30.29	gold quality
ascending aorta	UBERON:0001496	30.21	gold quality
islet of Langerhans	UBERON:0000006	29.85	gold quality
right adrenal gland	UBERON:0001233	29.80	gold quality
vermiform appendix	UBERON:0001154	29.35	gold quality
multicellular organism	UBERON:0000468	28.91	gold quality
cortex of kidney	UBERON:0001225	28.84	gold quality
lymph node	UBERON:0000029	28.77	gold quality
right adrenal gland cortex	UBERON:0035827	28.53	gold quality
left ovary	UBERON:0002119	28.34	gold quality
thoracic mammary gland	UBERON:0005200	28.24	silver quality
duodenum	UBERON:0002114	28.14	gold quality
fallopian tube	UBERON:0003889	27.95	gold quality
muscle of leg	UBERON:0001383	27.84	gold quality
stomach	UBERON:0000945	27.80	gold quality
adrenal tissue	UBERON:0018303	27.80	gold quality
adrenal gland	UBERON:0002369	27.72	gold quality
putamen	UBERON:0001874	27.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	27.31	gold quality
endometrium	UBERON:0001295	27.30	gold quality
gastrocnemius	UBERON:0001388	27.13	gold quality
body of stomach	UBERON:0001161	27.11	gold quality
left adrenal gland cortex	UBERON:0035825	27.02	gold quality
pancreas	UBERON:0001264	26.93	gold quality
superior frontal gyrus	UBERON:0002661	26.83	gold quality
body of uterus	UBERON:0009853	26.53	gold quality
left adrenal gland	UBERON:0001234	26.47	gold quality
kidney	UBERON:0002113	26.40	gold quality
right lobe of liver	UBERON:0001114	26.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	26.33	gold quality
heart	UBERON:0000948	26.27	gold quality
vagina	UBERON:0000996	26.13	gold quality
rectum	UBERON:0001052	26.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
heart left ventricle	UBERON:0002084	25.86	gold quality
small intestine	UBERON:0002108	25.67	gold quality
right frontal lobe	UBERON:0002810	25.67	silver quality
right lobe of thyroid gland	UBERON:0001119	25.61	gold quality
right atrium auricular region	UBERON:0006631	25.23	gold quality
Ammon’s horn	UBERON:0001954	24.96	gold quality
upper lobe of left lung	UBERON:0008952	24.80	silver quality
calcaneal tendon	UBERON:0003701	24.78	gold quality
omental fat pad	UBERON:0010414	24.77	gold quality
caudate nucleus	UBERON:0001873	24.75	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
intestine	UBERON:0000160	24.54	gold quality
saliva-secreting gland	UBERON:0001044	24.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	24.47	gold quality
body of pancreas	UBERON:0001150	24.35	gold quality
esophagus mucosa	UBERON:0002469	24.11	gold quality
fundus of stomach	UBERON:0001160	24.06	gold quality
colon	UBERON:0001155	23.99	gold quality
corpus callosum	UBERON:0002336	23.94	gold quality
metanephros cortex	UBERON:0010533	23.94	gold quality
prostate gland	UBERON:0002367	23.91	gold quality
minor salivary gland	UBERON:0001830	23.76	gold quality
hypothalamus	UBERON:0001898	23.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	23.47	gold quality
transverse colon	UBERON:0001157	23.33	gold quality
adult mammalian kidney	UBERON:0000082	23.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.27

HPA expression

RNA tissue specificity: Not detected

32 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	2.3
Cerebellum	tissue	2.1
Olfactory bulb	tissue	2.1
Cerebral cortex	tissue	1.6
Midbrain	tissue	1.6
Hippocampal formation	tissue	1.6
Entorhinal cortex	tissue	1.6
Occipital cortex	tissue	1.6
Insular cortex	tissue	1.6
Amygdala	tissue	1.5
Thalamus	tissue	1.5
Superior colliculi	tissue	1.5
Spinal cord	tissue	1.5
Ventral forebrain	tissue	1.5
Retrosplenial and cingulate cortex	tissue	1.5
Somatosensory cortex	tissue	1.5
Retrosplenial cortex	tissue	1.5
Motor cortex	tissue	1.4
Putamen	tissue	1.4
Substantia nigra	tissue	1.4
Basal ganglia	tissue	1.3
Medulla oblongata	tissue	1.3
Periaqueductal gray	tissue	1.3
Temporal cortex	tissue	1.3
Prefrontal cortex	tissue	1.2
Pons	tissue	1.2
Hypothalamus	tissue	1.2
Septum	tissue	1.2
Skin 1	tissue	0.3
Testis	tissue	0.2
Frontal cortex	tissue	0.1
Postcentral gyrus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 28; highest nTPM — White matter (2.3), Dorsal spinal cord (1.5), Subiculum (1.5), Ventral hippocampus (1.4), Ventral spinal cord (1.4).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 4.21e-15, LOEUF 1.04, missense Z 1.38 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000378832 — one region, missense o/e 0.91.

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Accsl	ENSMUSG00000075023
drosophila_melanogaster	CG1640	FBGN0030478
drosophila_melanogaster	CG6321	FBGN0036117
caenorhabditis_elegans		WBGENE00009232
caenorhabditis_elegans		WBGENE00010984
caenorhabditis_elegans		WBGENE00011436
caenorhabditis_elegans	C32F10.8	WBGENE00016333

Paralogs (7): AADAT (ENSG00000109576), ACCS (ENSG00000110455), KYAT3 (ENSG00000137944), GPT2 (ENSG00000166123), GPT (ENSG00000167701), KYAT1 (ENSG00000171097), TAT (ENSG00000198650)

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
Oryza sativa Indica Group	A2XLL2	100.0%	Diamond
Oryza sativa Japonica Group	Q10DK7	100.0%	Diamond
Cucurbita pepo	P23279	96.6%	Diamond
Cucurbita maxima	P23599	96.6%	Diamond
Arabidopsis thaliana	Q9LR30	93.1%	Diamond
Vigna radiata var. radiata	Q01912	92.4%	Diamond
Streptomyces avermitilis MA-4680 = NBRC 14893	Q82DR2	89.1%	Diamond
Solanum lycopersicum	P18485	88.3%	Diamond
Nicotiana tabacum	Q07262	88.3%	Diamond
Bos taurus	Q5E9H2	83.9%	Diamond
Malus domestica	P37821	74.9%	Diamond
Prunus mume	Q9MB95	69.8%	Diamond
Aspergillus terreus NIH2624	Q0CS62	69.2%	Diamond
Dianthus caryophyllus	P27486	66.3%	Diamond
Takifugu rubripes	Q9W698	58.0%	Diamond
Bacillus subtilis subsp. subtilis str. 168	Q795M6	48.6%	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
ALKBH3	protein-coding	221120
C11orf96	protein-coding	387763
ALKBH3-AS1	ncRNA	100507300
ACCS	protein-coding	84680
EXT2	protein-coding	2132
ALX4	protein-coding	60529
HSD17B12	protein-coding	51144

Protein

Protein identifiers

Probable inactive 1-aminocyclopropane-1-carboxylate synthase-like protein 2 — Q4AC99 (reviewed: Q4AC99)

All UniProt accessions (2): Q4AC99, E9PI59

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.

RefSeq proteins (2): NP_001027025, NP_001350042 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR050478	Ethylene_sulfur-biosynth	Family

Pfam: PF00155

UniProt features (10 total): sequence conflict 6, chain 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4AC99-F1	84.52	0.68

Human Protein Atlas

Protein class: Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IF approved

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 (1)

Type	Positions
N6-(pyridoxal phosphate)lysine	395

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: 24 (showing top): GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_NITROGENOUS_GROUPS, GOMF_VITAMIN_BINDING, YOSHIMURA_MAPK8_TARGETS_UP, MIKKELSEN_MCV6_ICP_WITH_H3K27ME3, GOMF_VITAMIN_B6_BINDING, GSE10094_LCMV_VS_LISTERIA_IND_EFF_CD4_TCELL_DN, GSE11924_TH2_VS_TH17_CD4_TCELL_UP, GSE14350_IL2RB_KO_VS_WT_TREG_UP, GSE18148_CBFB_KO_VS_WT_TREG_DN, GOMF_TRANSAMINASE_ACTIVITY, GSE39820_TGFBETA1_VS_TGFBETA3_IN_IL6_IL23A_TREATED_CD4_TCELL_UP, GSE2585_CD80_HIGH_VS_LOW_AIRE_KO_MTEC_DN, GSE4811_CLASSSICALY_ACTIVATED_VS_TYPE_2_ACTIVATED_MACROPHAGE_UP, GSE5503_LIVER_DC_VS_MLN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, GSE21670_UNTREATED_VS_TGFB_TREATED_CD4_TCELL_UP

GO Biological Process (2): amino acid metabolic process (GO:0006520), biosynthetic process (GO:0009058)

GO Molecular Function (2): transaminase activity (GO:0008483), pyridoxal phosphate binding (GO:0030170)

GO top-level categories

5 GO namespaces:

Category	Terms
primary metabolic process	1
metabolic process	1
transferase activity, transferring nitrogenous groups	1
anion binding	1
vitamin B6 binding	1

Protein interactions and networks

STRING

showing 16 of 867 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACCSL	DEFB112	Q30KQ8	395
ACCSL	OR51B2	Q9Y5P1	388
ACCSL	AIPL1	Q9NZN9	369
ACCSL	AASDH	Q4L235	368
ACCSL	ST8SIA3	O43173	364
ACCSL	PATL2	C9JE40	355
ACCSL	MOCOS	Q96EN8	350
ACCSL	WDR38	Q5JTN6	349
ACCSL	SLC15A5	A6NIM6	332
ACCSL	BTG4	Q9NY30	321
ACCSL	DCLK3	Q9C098	314
ACCSL	TCF23	Q7RTU1	311
ACCSL	TMEM255B	Q8WV15	306
ACCSL	RAB6C	Q9H0N0	303
ACCSL	LRRC14	Q15048	302
ACCSL	FHAD1	B1AJZ9	302

IntAct

BioGRID (3 interactions; top human partners by supporting records): CSK (Synthetic Lethality), PARP9 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for ACCSL: 91 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	82
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
148316	GRCh38/hg38 11p12-11.12(chr11:39179252-49135735)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACCSL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 954):

Position(s)	Effect	Δscore	Sites
11:44051651–44051652	acceptor_loss	1.0000	5
11:44052989–44052990	acceptor_loss	1.0000	4
11:44053069–44053070	donor_loss	1.0000	5
11:44053405	acceptor_loss	1.0000
11:44055190	acceptor_gain	1.0000
11:44055200–44055201	acceptor_loss	1.0000	5
11:44056327–44056328	donor_loss	1.0000	4
11:44058308	acceptor_gain	1.0000
11:44058312	acceptor_gain	1.0000
11:44058315	acceptor_loss	1.0000	3

AlphaMissense

305 missense substitutions predicted likely pathogenic (of 3,756 scored), across 132 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
G209	6	0.895	0.947
Q432	6	0.818	0.890
F528	5	0.849	0.944
F347	5	0.833	0.921
W444	5	0.786	0.848
Y204	5	0.740	0.855
E359	5	0.704	0.852
F220	4	0.862	0.897
S374	4	0.826	0.874
F507	4	0.826	0.833
F532	4	0.820	0.904
W391	4	0.778	0.840
R138	4	0.774	0.866
F421	4	0.761	0.818
F397	4	0.760	0.813
S394	4	0.750	0.799
F546	4	0.750	0.754
W485	4	0.721	0.817
W527	4	0.721	0.779
W207	4	0.689	0.796

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST007096_162	Pulse pressure	1e-9
GCST007269_319	Pulse pressure	1e-9

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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