AGTPBP1

Summary

AGTPBP1 (ATP/GTP binding carboxypeptidase 1, HGNC:17258) is a protein-coding gene on chromosome 9q21.33, encoding Cytosolic carboxypeptidase 1 (Q9UPW5). Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins.

NNA1 is a zinc carboxypeptidase that contains nuclear localization signals and an ATP/GTP-binding motif that was initially cloned from regenerating spinal cord neurons of the mouse.

Source: NCBI Gene 23287 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodegeneration, childhood-onset, with cerebellar atrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 206 total — 15 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes
• MANE Select transcript: NM_001330701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17258
Approved symbol	AGTPBP1
Name	ATP/GTP binding carboxypeptidase 1
Location	9q21.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1035, Nna1, CCP1
Ensembl gene	ENSG00000135049
Ensembl biotype	protein_coding
OMIM	606830
Entrez	23287

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 28 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000337006, ENST00000357081, ENST00000376080, ENST00000376081, ENST00000376083, ENST00000489265, ENST00000491784, ENST00000628899, ENST00000901874, ENST00000901875, ENST00000901876, ENST00000901877, ENST00000901878, ENST00000901879, ENST00000901880, ENST00000901881, ENST00000901882, ENST00000901883, ENST00000901884, ENST00000901885, ENST00000912526, ENST00000912527, ENST00000912528, ENST00000912529, ENST00000912530, ENST00000912531, ENST00000950849, ENST00000950850, ENST00000950851, ENST00000950852, ENST00000950853, ENST00000950854

RefSeq mRNA: 4 — MANE Select: NM_001330701 NM_001286715, NM_001286717, NM_001330701, NM_015239

CCDS: CCDS6672, CCDS69615, CCDS75854, CCDS83382

Canonical transcript exons

ENST00000357081 — 26 exons

Exon	Start	End
ENSE00001401195	85741775	85741954
ENSE00001681884	85655143	85655320
ENSE00001767652	85546539	85547286
ENSE00003465751	85575315	85575475
ENSE00003493058	85660936	85660973
ENSE00003505864	85681268	85681335
ENSE00003521802	85678335	85678398
ENSE00003602976	85672550	85672681
ENSE00003644737	85677436	85677582
ENSE00003658994	85669485	85669578
ENSE00003714499	85588298	85588478
ENSE00003716265	85692689	85692813
ENSE00003720529	85596362	85596449
ENSE00003731958	85632662	85633374
ENSE00003732854	85642827	85642943
ENSE00003733628	85592560	85592704
ENSE00003733936	85589528	85589681
ENSE00003736880	85657435	85657643
ENSE00003745202	85585463	85585594
ENSE00003748217	85618983	85619131
ENSE00003750495	85646321	85646418
ENSE00003751005	85621202	85621285
ENSE00003752887	85619215	85619301
ENSE00003753921	85578920	85579096
ENSE00003754747	85586831	85586960
ENSE00003769184	85712502	85712566

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0480 / max 741.5628, expressed in 1705 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101188	14.9426	1703
101187	0.1055	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.22	gold quality
corpus callosum	UBERON:0002336	96.42	gold quality
monocyte	CL:0000576	95.71	gold quality
mononuclear cell	CL:0000842	95.69	gold quality
leukocyte	CL:0000738	95.43	gold quality
bone marrow	UBERON:0002371	94.82	gold quality
bone marrow cell	CL:0002092	93.79	gold quality
inferior olivary complex	UBERON:0002127	93.65	gold quality
trabecular bone tissue	UBERON:0002483	93.33	gold quality
heart right ventricle	UBERON:0002080	92.91	gold quality
blood	UBERON:0000178	92.50	gold quality
substantia nigra pars compacta	UBERON:0001965	92.41	gold quality
cranial nerve II	UBERON:0000941	92.17	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.03	gold quality
pons	UBERON:0000988	91.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.67	gold quality
endothelial cell	CL:0000115	91.51	gold quality
postcentral gyrus	UBERON:0002581	91.38	gold quality
spinal cord	UBERON:0002240	91.29	gold quality
superior frontal gyrus	UBERON:0002661	91.07	gold quality
inferior vagus X ganglion	UBERON:0005363	90.97	gold quality
subthalamic nucleus	UBERON:0001906	90.77	gold quality
parietal lobe	UBERON:0001872	90.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.69	gold quality
entorhinal cortex	UBERON:0002728	90.60	gold quality
granulocyte	CL:0000094	90.57	gold quality
prefrontal cortex	UBERON:0000451	90.57	gold quality
substantia nigra	UBERON:0002038	90.52	gold quality
medulla oblongata	UBERON:0001896	90.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting AGTPBP1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6844	99.82	70.69	2423

Literature-anchored findings (GeneRIF, showing 8)

• Data indicate that a functional nuclear export signals (NESs) in CCP1 that mediates direct binding to the export receptor CRM1. (PMID:23242554)
• we identified seven new putative CCP1 substrates, all of them harboring acidic amino acids in their gene-encoded C terminus (PMID:25381060)
• biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile-onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. (PMID:30420557)
• We conclude that complete loss-of-function of AGTPBP1 in humans, just like in mice and sheep, is associated with cerebellar and motor neuron disease, reminiscent of Pontocerebellar Hypoplasia Type 1 (PCH1). (PMID:30976113)
• A novel pathogenic variant in the 3’ end of the AGTPBP1 gene gives rise to neurodegeneration without cerebellar atrophy: an expansion of the disease phenotype? (PMID:33909173)
• The AGTPBP1 gene in neurobiology. (PMID:34637898)
• Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects. (PMID:37937809)
• Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway. (PMID:39129004)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agtpbp1	ENSDARG00000105214
mus_musculus	Agtpbp1	ENSMUSG00000021557
rattus_norvegicus	Agtpbp1	ENSRNOG00000018651

Paralogs (5): AGBL5 (ENSG00000084693), AGBL3 (ENSG00000146856), AGBL2 (ENSG00000165923), AGBL4 (ENSG00000186094), AGBL1 (ENSG00000273540)

Protein

Protein identifiers

Cytosolic carboxypeptidase 1 — Q9UPW5 (reviewed: Q9UPW5)

Alternative names: ATP/GTP-binding protein 1, Nervous system nuclear protein induced by axotomy protein 1 homolog, Protein deglutamylase CCP1

All UniProt accessions (2): Q9UPW5, J3KNS1

UniProt curated annotations — full annotation on UniProt →

Function. Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK. Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis.

Subunit / interactions. Interacts with MYLK.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Mitochondrion.

Disease relevance. Neurodegeneration, childhood-onset, with cerebellar atrophy (CONDCA) [MIM:618276] An autosomal recessive disorder characterized by early onset of progressive neurodegeneration affecting the central and peripheral nervous systems. Clinical features include global developmental delay, impaired intellectual development, poor or absent speech, and motor abnormalities. Brain imaging shows cerebellar atrophy. Death in childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UPW5-1	1	yes
Q9UPW5-2	2
Q9UPW5-3	3

RefSeq proteins (4): NP_001273644, NP_001273646, NP_001317630, NP_056054 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR033852	CBPC1/4	Domain
IPR040626	Pepdidase_M14_N	Domain
IPR050821	Cytosolic_carboxypeptidase	Family

Pfam: PF00246, PF18027, PF25571

Enzyme classification (BRENDA):

• EC 3.4.17.24 — tubulin-glutamate carboxypeptidase (BRENDA: 5 organisms, 60 substrates, 5 inhibitors, 4 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BIOTIN-GLU-GLU	0.15	1
BIOTIN-GLU-GLU-GLU	0.18	1
BIOTIN-GLU-GLU-GLU-GLY-GLU-GLU	0.074	1
BIOTIN-GLU-GLU-GLY-GLU-GLU-GLU	0.076	1

Catalyzed reactions (Rhea), 2 shown:

• (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + H2O = (L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + L-glutamate (RHEA:60004)
• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-[tubulin] + L-glutamate (RHEA:63792)

UniProt features (35 total): sequence conflict 14, sequence variant 10, binding site 3, splice variant 2, region of interest 2, chain 1, domain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPW5-F1	75.95	0.54

Functional residue map

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

Catalytic / active sites (1): 1102 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 920; 923; 1017

Post-translational modifications (1): 1168

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 319 (showing top): WENDT_COHESIN_TARGETS_UP, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_BEHAVIOR, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_ADULT_BEHAVIOR, GOBP_CEREBELLAR_PURKINJE_CELL_LAYER_FORMATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CEREBELLAR_CORTEX_MORPHOGENESIS, GOBP_NEUROGENESIS

GO Biological Process (19): eye photoreceptor cell differentiation (GO:0001754), proteolysis (GO:0006508), mitochondrion organization (GO:0007005), adult walking behavior (GO:0007628), negative regulation of cell population proliferation (GO:0008285), cerebellar Purkinje cell differentiation (GO:0021702), olfactory bulb development (GO:0021772), central nervous system neuron development (GO:0021954), protein deglutamylation (GO:0035608), C-terminal protein deglutamylation (GO:0035609), protein side chain deglutamylation (GO:0035610), neuromuscular process (GO:0050905), retina development in camera-type eye (GO:0060041), anterograde axonal transport of mitochondrion (GO:0098957), retrograde axonal transport of mitochondrion (GO:0098958), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), cerebellum development (GO:0021549), cerebellar Purkinje cell layer development (GO:0021680), axonal transport (GO:0098930)

GO Molecular Function (8): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), axon cytoplasm (GO:1904115), axon (GO:0030424)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	4
cellular anatomical structure	4
central nervous system neuron differentiation	2
protein deglutamylation	2
axonal transport of mitochondrion	2
axon	2
intracellular membrane-bounded organelle	2
cytoplasm	2
photoreceptor cell differentiation	1
eye morphogenesis	1
protein metabolic process	1
organelle organization	1
adult locomotory behavior	1
walking behavior	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell differentiation in hindbrain	1
cerebellar Purkinje cell layer formation	1
olfactory lobe development	1
neuron development	1
peptidyl-glutamic acid modification	1
C-terminal protein amino acid modification	1
nervous system process	1
camera-type eye development	1
anterograde axonal transport	1
retrograde axonal transport	1
ubiquitin-dependent protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
metencephalon development	1
cerebellar cortex development	1
axo-dendritic transport	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
cytoskeletal protein binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGTPBP1	CPXM2	Q8N436	668
AGTPBP1	TTL	Q8NG68	650
AGTPBP1	TTLL1	O95922	612
AGTPBP1	TTLL5	Q6EMB2	560
AGTPBP1	SVBP	Q8N300	480
AGTPBP1	TTLL4	Q14679	479
AGTPBP1	TTLL10	Q6ZVT0	463
AGTPBP1	TTLL7	Q6ZT98	440
AGTPBP1	TTLL11	Q8NHH1	434
AGTPBP1	NAA35	Q5VZE5	433
AGTPBP1	SUDS3	Q9H7L9	408
AGTPBP1	CLP1	Q92989	392
AGTPBP1	TTLL12	Q14166	385
AGTPBP1	ASPA	P45381	381
AGTPBP1	TBC1D20	Q96BZ9	378

IntAct

48 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
RNPS1	CASC3	psi-mi:“MI:0914”(association)	0.530
AGTPBP1	LRPAP1	psi-mi:“MI:0915”(physical association)	0.400
AGTPBP1	TTLL4	psi-mi:“MI:0915”(physical association)	0.400
FOXK1	PHKG2	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
RNPS1	C1orf226	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
FGF12	SUPT5H	psi-mi:“MI:0914”(association)	0.350
RASA2	DKC1	psi-mi:“MI:0914”(association)	0.350
ZC2HC1B	TUBB4A	psi-mi:“MI:0914”(association)	0.350
INO80E	CHD1	psi-mi:“MI:0914”(association)	0.350
RPL22	CENPB	psi-mi:“MI:0914”(association)	0.350
SYT2	SMAP	psi-mi:“MI:0914”(association)	0.350
TMOD1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SLC4A2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
SLC4A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
PHLPP1	AIP	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (73): AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Proximity Label-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Proximity Label-MS), AGTPBP1 (Affinity Capture-MS), TTLL4 (Affinity Capture-MS), AGTPBP1 (Reconstituted Complex), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), AGTPBP1 (Proximity Label-MS)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

Diamond homologs: A6H8T7, A9JRL3, B2GV17, D2GXM8, E1B9D8, E1C3P4, O76373, Q09296, Q09LZ8, Q09M02, Q09M05, Q0P4M4, Q4R632, Q4U2V3, Q5U5Z8, Q5VU57, Q641K1, Q6DD21, Q8CDK2, Q8CDP0, Q8I2A6, Q8NDL9, Q8NEM8, Q96MI9, Q9UPW5, Q9VY99, Q58CX9, B0JZV4, Q68EI3, P30795, A0A096LPI5, Q8N976, Q96MD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	10
Uncertain significance	130
Likely benign	12
Benign	7

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
2506865	NM_001330701.2(AGTPBP1):c.1182del (p.Phe394fs)	Pathogenic
2577529	NM_001330701.2(AGTPBP1):c.910-1G>A	Pathogenic
3340642	NM_001330701.2(AGTPBP1):c.988C>T (p.Arg330Ter)	Pathogenic
3772519	NM_001330701.2(AGTPBP1):c.3349C>T (p.Gln1117Ter)	Pathogenic
522816	NM_001330701.2(AGTPBP1):c.2336-1G>T	Pathogenic
522817	NM_001286715.1(AGTPBP1):c.2892del (p.Tyr964Terfs)	Pathogenic
599365	NM_001330701.2(AGTPBP1):c.2566C>T (p.Gln856Ter)	Pathogenic
599366	NM_001330701.2(AGTPBP1):c.2552C>T (p.Thr851Met)	Pathogenic
599367	NM_001330701.2(AGTPBP1):c.2969A>T (p.His990Leu)	Pathogenic
599370	NM_001330701.2(AGTPBP1):c.2080T>G (p.Tyr694Asp)	Pathogenic
599381	NM_001330701.2(AGTPBP1):c.2842C>T (p.Arg948Ter)	Pathogenic
625637	GRCh37/hg19 9q21.2-22.32(chr9:79520825-97201274)	Pathogenic
983189	GRCh37/hg19 9q21.33(chr9:88201316-88224515)x1	Pathogenic
983264	NM_001330701.2(AGTPBP1):c.1240C>T (p.Arg414Ter)	Pathogenic
984979	NM_001330701.2(AGTPBP1):c.820_821del (p.Gln274fs)	Pathogenic
1029296	NM_001330701.2(AGTPBP1):c.1606C>T (p.Arg536Ter)	Likely pathogenic
1323865	NM_001330701.2(AGTPBP1):c.2481T>A (p.Tyr827Ter)	Likely pathogenic
2440454	NM_001330701.2(AGTPBP1):c.-34+1G>A	Likely pathogenic
2444496	NM_001330701.2(AGTPBP1):c.2833C>T (p.Gln945Ter)	Likely pathogenic
2690507	NM_001330701.2(AGTPBP1):c.2016-2A>G	Likely pathogenic
3360665	NM_001330701.2(AGTPBP1):c.3504-1G>T	Likely pathogenic
599368	NM_001330701.2(AGTPBP1):c.2362C>T (p.Gln788Ter)	Likely pathogenic
599379	NM_001330701.2(AGTPBP1):c.2186+2T>G	Likely pathogenic
599380	NM_001330701.2(AGTPBP1):c.2195A>G (p.Tyr732Cys)	Likely pathogenic
983265	NM_001330701.2(AGTPBP1):c.2396G>T (p.Arg799Leu)	Likely pathogenic

SpliceAI

5359 predictions. Top by Δscore:

Variant	Effect	Δscore
9:85547287:C:CC	acceptor_gain	1.0000
9:85547294:C:CT	acceptor_gain	1.0000
9:85547295:A:T	acceptor_gain	1.0000
9:85549681:T:TA	donor_gain	1.0000
9:85575311:CTACC:C	donor_loss	1.0000
9:85575313:ACCT:A	donor_loss	1.0000
9:85575314:C:G	donor_loss	1.0000
9:85575314:CCTAG:C	donor_gain	1.0000
9:85575472:AACC:A	acceptor_gain	1.0000
9:85575473:ACC:A	acceptor_gain	1.0000
9:85575474:CC:C	acceptor_gain	1.0000
9:85575474:CCC:C	acceptor_gain	1.0000
9:85575475:CCT:C	acceptor_gain	1.0000
9:85575476:C:CC	acceptor_gain	1.0000
9:85575476:C:T	acceptor_gain	1.0000
9:85575477:T:C	acceptor_gain	1.0000
9:85575477:T:TC	acceptor_gain	1.0000
9:85586965:A:C	acceptor_gain	1.0000
9:85586971:A:C	acceptor_gain	1.0000
9:85592702:TTT:T	acceptor_gain	1.0000
9:85596357:CTT:C	donor_loss	1.0000
9:85596358:TTACT:T	donor_loss	1.0000
9:85596359:TA:T	donor_loss	1.0000
9:85596360:A:AC	donor_gain	1.0000
9:85596361:C:CT	donor_gain	1.0000
9:85596361:CT:C	donor_gain	1.0000
9:85596361:CTT:C	donor_gain	1.0000
9:85596361:CTTA:C	donor_gain	1.0000
9:85596361:CTTAT:C	donor_gain	1.0000
9:85596445:CATAC:C	acceptor_gain	1.0000

AlphaMissense

8101 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:85575439:C:G	G1127R	1.000
9:85575439:C:T	G1127R	1.000
9:85578956:C:A	E1102D	1.000
9:85578956:C:G	E1102D	1.000
9:85578957:T:A	E1102V	1.000
9:85578958:C:T	E1102K	1.000
9:85578968:A:C	S1098R	1.000
9:85578968:A:T	S1098R	1.000
9:85578970:T:G	S1098R	1.000
9:85578994:A:G	W1090R	1.000
9:85578994:A:T	W1090R	1.000
9:85579002:A:T	V1087D	1.000
9:85585550:A:C	F1026L	1.000
9:85585550:A:T	F1026L	1.000
9:85585551:A:G	F1026S	1.000
9:85585552:A:G	F1026L	1.000
9:85585571:A:C	H1019Q	1.000
9:85585571:A:T	H1019Q	1.000
9:85585573:G:C	H1019D	1.000
9:85585575:C:A	G1018V	1.000
9:85585575:C:T	G1018D	1.000
9:85585576:C:G	G1018R	1.000
9:85585579:G:C	H1017D	1.000
9:85585584:T:A	D1015V	1.000
9:85586918:C:A	W982C	1.000
9:85586918:C:G	W982C	1.000
9:85586920:A:G	W982R	1.000
9:85586920:A:T	W982R	1.000
9:85586927:A:C	N979K	1.000
9:85586927:A:T	N979K	1.000

dbSNP variants (sampled 300 via entrez): RS1000086199 (9:85751724 C>T), RS1000096199 (9:85799347 A>G), RS1000102773 (9:85691530 A>C), RS1000109248 (9:85611904 A>T), RS1000121986 (9:85635156 C>T), RS1000126645 (9:85589978 A>G), RS1000126893 (9:85668344 T>TA), RS1000152120 (9:85575022 T>A,C), RS1000183953 (9:85574811 T>A,G), RS1000192683 (9:85641209 A>G,T), RS1000199542 (9:85723660 G>A), RS1000231854 (9:85728326 A>C), RS1000254840 (9:85685852 T>G), RS1000257783 (9:85717785 C>A,T), RS1000270188 (9:85631945 A>G,T)

Disease associations

OMIM: gene MIM:606830 | disease phenotypes: MIM:618276, MIM:618056

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodegeneration, childhood-onset, with cerebellar atrophy	Definitive	Autosomal recessive
pontocerebellar hypoplasia type 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neurodegeneration, childhood-onset, with cerebellar atrophy	Definitive	AR

Mondo (4): neurodegeneration, childhood-onset, with cerebellar atrophy (MONDO:0032650), neurodevelopmental disorder with cerebellar atrophy and with or without seizures (MONDO:0020841), motor peripheral neuropathy (MONDO:0002316), pontocerebellar hypoplasia type 1 (MONDO:0016396)

Orphanet (0):

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000486	Strabismus
HP:0000514	Slow saccadic eye movements
HP:0000529	Progressive visual loss
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000817	Reduced eye contact
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002120	Cerebral cortical atrophy
HP:0002273	Tetraparesis
HP:0002283	Global brain atrophy
HP:0002350	Cerebellar cyst
HP:0002376	Developmental regression
HP:0002398	Degeneration of anterior horn cells

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007325_215	General risk tolerance (MTAG)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C548069	Pontocerebellar Hypoplasia Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523495 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	increases expression	1
Bortezomib	increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	affects expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Lead	affects splicing	1
Naled	affects expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4413971	Binding	Inhibition of human CCP1 at 1 nM to mM using tubulin as substrate preincubated for 45 mins measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	Synthesis and Structural/Functional Characterization of Selective M14 Metallocarboxypeptidase Inhibitors Based on Phosphinic Pseudopeptide Scaffold: Implications on the Design of Specific Optical Probes. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.