AFG2B

Summary

AFG2B (AAA ATPase AFG2B, HGNC:28762) is a protein-coding gene on chromosome 15q21.1, encoding ATPase family gene 2 protein homolog B (Q9BVQ7). ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. It is a common-essential gene (DepMap: required in 95.7% of cancer cell lines).

Enables identical protein binding activity and preribosome binding activity. Involved in ribosomal large subunit biogenesis. Located in cytoplasm and spindle. Implicated in autosomal recessive nonsyndromic deafness.

Source: NCBI Gene 79029 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 119 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 186 total — 9 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 32
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 95.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_024063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28762
Approved symbol	AFG2B
Name	AAA ATPase AFG2B
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC5347, FLJ12286
Ensembl gene	ENSG00000171763
Ensembl biotype	protein_coding
OMIM	619578
Entrez	79029

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000305560, ENST00000525552, ENST00000531624, ENST00000531970, ENST00000533199, ENST00000533841, ENST00000559860, ENST00000907461, ENST00000960280

RefSeq mRNA: 2 — MANE Select: NM_024063 NM_001323640, NM_024063

CCDS: CCDS10123, CCDS81877

Canonical transcript exons

ENST00000305560 — 8 exons

Exon	Start	End
ENSE00001120480	45415587	45415779
ENSE00001311033	45421043	45421415
ENSE00001317960	45402336	45403518
ENSE00003663692	45418557	45418682
ENSE00003677890	45417269	45417399
ENSE00003726855	45410372	45410530
ENSE00003729018	45414571	45414780
ENSE00003737947	45405320	45405505

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 92.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0577 / max 129.3518, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146434	5.9756	1680
146433	3.0821	1426

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.43	gold quality
esophagus squamous epithelium	UBERON:0006920	91.50	gold quality
buccal mucosa cell	CL:0002336	91.48	gold quality
ventricular zone	UBERON:0003053	90.87	gold quality
secondary oocyte	CL:0000655	90.68	gold quality
epithelium of esophagus	UBERON:0001976	90.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.28	gold quality
esophagus mucosa	UBERON:0002469	88.10	gold quality
amniotic fluid	UBERON:0000173	88.06	gold quality
squamous epithelium	UBERON:0006914	87.84	gold quality
jejunal mucosa	UBERON:0000399	87.72	gold quality
ganglionic eminence	UBERON:0004023	87.43	gold quality
oral cavity	UBERON:0000167	86.81	gold quality
embryo	UBERON:0000922	86.80	gold quality
mucosa of transverse colon	UBERON:0004991	86.34	gold quality
cortical plate	UBERON:0005343	86.18	gold quality
cervix squamous epithelium	UBERON:0006922	86.15	silver quality
duodenum	UBERON:0002114	86.02	gold quality
oocyte	CL:0000023	85.73	gold quality
skin of leg	UBERON:0001511	85.67	gold quality
cerebellar hemisphere	UBERON:0002245	85.52	gold quality
cerebellar cortex	UBERON:0002129	85.35	gold quality
sperm	CL:0000019	85.27	gold quality
left ovary	UBERON:0002119	84.98	gold quality
vagina	UBERON:0000996	84.83	gold quality
esophagus	UBERON:0001043	84.82	gold quality
skin of abdomen	UBERON:0001416	84.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	122.74
E-ANND-3	no	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting AFG2B, 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-4692	100.00	67.32	2066
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-595	98.25	67.44	699
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-5579-3P	97.00	68.81	1111
HSA-MIR-4633-5P	96.17	66.36	501

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss. (PMID:34626583)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	afg2b	ENSDARG00000061763
mus_musculus	Afg2b	ENSMUSG00000118663
rattus_norvegicus	Afg2b	ENSRNOG00000000169
drosophila_melanogaster	CG12010	FBGN0035443
caenorhabditis_elegans		WBGENE00007352
caenorhabditis_elegans		WBGENE00008053

Paralogs (5): PEX6 (ENSG00000124587), PEX1 (ENSG00000127980), NVL (ENSG00000143748), AFG2A (ENSG00000145375), VCP (ENSG00000165280)

Protein

Protein identifiers

ATPase family gene 2 protein homolog B — Q9BVQ7 (reviewed: Q9BVQ7)

Alternative names: AFG2 AAA ATPase homolog B, Ribosome biogenesis protein SPATA5L1, Spermatogenesis-associated protein 5-like protein 1

All UniProt accessions (3): Q9BVQ7, H0YCA5, H0YL79

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity. Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles.

Subunit / interactions. Part of the 55LCC heterohexameric ATPase complex composed at least of AIRIM, AFG2A, AFG2B and CINP. Associates with pre-60S ribosomal particles.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Nucleus.

Tissue specificity. Expressed in both neurons and glia during embryonic and adult stages of brain development.

Disease relevance. Deafness, autosomal recessive, 119 (DFNB119) [MIM:619615] A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with hearing loss and spasticity (NEDHLS) [MIM:619616] An autosomal recessive neurodevelopmental disorder characterized by hearing loss, global developmental delay, impaired intellectual development, hypotonia, spastic-dystonic cerebral palsy, focal or generalized epilepsy, and microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. In the context of 55LCC heterohexameric ATPase complex, the ATPase activity is stimulated by DNA binding and inhibited in presence of RNA.

Similarity. Belongs to the AAA ATPase family. AFG2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BVQ7-1	1	yes
Q9BVQ7-2	2
Q9BVQ7-3	3

RefSeq proteins (2): NP_001310569, NP_076968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041569	AAA_lid_3	Domain
IPR050168	AAA_ATPase_domain	Family

Pfam: PF00004, PF17862

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (35 total): sequence variant 24, splice variant 4, region of interest 2, binding site 2, chain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9LGO	ELECTRON MICROSCOPY	3.51
8RHN	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVQ7-F1	77.37	0.13

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 (2): 241–248; 505–512

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RIBOSOME_BIOGENESIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MACROAUTOPHAGY, WEI_MYCN_TARGETS_WITH_E_BOX, CADWELL_ATG16L1_TARGETS_DN, GOBP_MITOTIC_CELL_CYCLE, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY

GO Biological Process (6): retrograde protein transport, ER to cytosol (GO:0030970), ribosomal large subunit biogenesis (GO:0042273), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), mitotic spindle disassembly (GO:0051228), autophagosome maturation (GO:0097352), ribosome biogenesis (GO:0042254)

GO Molecular Function (9): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), polyubiquitin modification-dependent protein binding (GO:0031593), identical protein binding (GO:0042802), preribosome binding (GO:1990275), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), protein-containing complex binding (GO:0044877)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), VCP-NPL4-UFD1 AAA ATPase complex (GO:0034098), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoprotein complex biogenesis	2
binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
ribosome biogenesis	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
mitotic cell cycle	1
mitotic spindle organization	1
spindle disassembly	1
macroautophagy	1
protein-containing complex disassembly	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
modification-dependent protein binding	1
protein binding	1
ribonucleoprotein complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1
endoplasmic reticulum membrane	1
UFD1-NPL4 complex	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1

Protein interactions and networks

STRING

3109 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AFG2B	SHROOM3	Q8TF72	630
AFG2B	GATM	P50440	585
AFG2B	UMOD	P07911	483
AFG2B	AFG2A	Q8NB90	471
AFG2B	CST9	Q5W186	442
AFG2B	INTS15	Q96N11	397
AFG2B	YJEFN3	A6XGL0	396
AFG2B	SPATA13	Q96N96	393
AFG2B	CST9L	Q9H4G1	392
AFG2B	SAMD10	Q9BYL1	385
AFG2B	RSL24D1	Q9UHA3	381
AFG2B	MOSPD2	Q8NHP6	368
AFG2B	EEF1AKMT2	Q5JPI9	365
AFG2B	NOAZFP	Q9Y3S2	358
AFG2B	ZNF605	Q86T29	357

IntAct

90 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
POLD3	POLD1	psi-mi:“MI:0914”(association)	0.900
CINP	AFG2A	psi-mi:“MI:0914”(association)	0.830
AFG2A	AFG2B	psi-mi:“MI:0915”(physical association)	0.800
AFG2A	AFG2B	psi-mi:“MI:0407”(direct interaction)	0.800
AFG2B	AFG2A	psi-mi:“MI:0914”(association)	0.800
AFG2A	AFG2B	psi-mi:“MI:0914”(association)	0.800
AIRIM	AFG2A	psi-mi:“MI:0914”(association)	0.720
IFT81	NDC80	psi-mi:“MI:0914”(association)	0.640
NSA2	GNL2	psi-mi:“MI:0914”(association)	0.640
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
CINP	CHMP2A	psi-mi:“MI:0914”(association)	0.530
CAMKMT	COL1A1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
AFG2B	AFG2B	psi-mi:“MI:0407”(direct interaction)	0.520
AFG2A	RFC1	psi-mi:“MI:0915”(physical association)	0.500
AFG2B	RFC1	psi-mi:“MI:0914”(association)	0.460
AFG2B	STK4	psi-mi:“MI:0915”(physical association)	0.370
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Ppp6r1	PPP6C	psi-mi:“MI:0914”(association)	0.350

BioGRID (142): SPATA5L1 (Affinity Capture-RNA), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

Diamond homologs: A0A061IR73, A0A7N9VSG0, A4G0S4, A6UQT3, A6VHR1, A7YSY2, A9A916, C4QXI8, C4R6C2, D1CDT8, D4A2B7, G1X4S3, G1X7C7, G3GXG9, O05209, O13764, O14325, O15381, O18413, O26824, O28303, O28972, O43933, O60058, O74941, P03974, P23787, P24004, P25694, P32794, P33289, P33760, P34124, P36966, P41836, P46462, P46463, P46468, P54609, P54774

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SPATA5L1	“form complex”	“SPATA5-SPATA5L1 ATPase complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	11
Uncertain significance	127
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1275866	NM_024063.3(AFG2B):c.1826C>G (p.Ser609Ter)	Pathogenic
1321878	NM_024063.3(AFG2B):c.2147_2148del (p.Gln716fs)	Pathogenic
2671612	Single allele	Pathogenic
3065737	NM_024063.3(AFG2B):c.1304_1305del (p.Ile435fs)	Pathogenic
395389	GRCh37/hg19 15q15.1-21.2(chr15:41689327-52446981)x1	Pathogenic
4279329	GRCh37/hg19 15q21.1-21.2(chr15:45043912-51196595)x1	Pathogenic
4788723	NM_024063.3(AFG2B):c.1489_1490del (p.Gln497fs)	Pathogenic
976741	NM_024063.3(AFG2B):c.1090-2A>G	Pathogenic
976746	NM_024063.3(AFG2B):c.2176_2177del (p.Val726fs)	Pathogenic
1185569	NM_024063.3(AFG2B):c.1313T>C (p.Leu438Pro)	Likely pathogenic
1210110	NM_024063.3(AFG2B):c.1676del (p.Ala559fs)	Likely pathogenic
1210111	NM_024063.3(AFG2B):c.1682T>C (p.Leu561Ser)	Likely pathogenic
1210112	NM_024063.3(AFG2B):c.85T>G (p.Cys29Gly)	Likely pathogenic
1210149	NM_024063.3(AFG2B):c.2066G>T (p.Gly689Val)	Likely pathogenic
1275861	NM_024063.3(AFG2B):c.734T>A (p.Val245Glu)	Likely pathogenic
1275865	NM_024063.3(AFG2B):c.190C>T (p.Arg64Trp)	Likely pathogenic
3901187	NM_024063.3(AFG2B):c.809T>C (p.Leu270Pro)	Likely pathogenic
4075437	NM_024063.3(AFG2B):c.1924G>T (p.Gly642Ter)	Likely pathogenic
976744	NM_024063.3(AFG2B):c.1973G>A (p.Arg658Lys)	Likely pathogenic
976745	NM_024063.3(AFG2B):c.2006T>G (p.Met669Arg)	Likely pathogenic

SpliceAI

1112 predictions. Top by Δscore:

Variant	Effect	Δscore
15:45405306:T:TA	acceptor_gain	1.0000
15:45405315:TATA:T	acceptor_loss	1.0000
15:45405317:TAGGT:T	acceptor_loss	1.0000
15:45405318:AGGT:A	acceptor_gain	1.0000
15:45405319:G:GT	acceptor_loss	1.0000
15:45405319:GGTG:G	acceptor_gain	1.0000
15:45405502:GAAG:G	donor_gain	1.0000
15:45405503:AAGG:A	donor_loss	1.0000
15:45405504:AGGT:A	donor_loss	1.0000
15:45405505:GGT:G	donor_loss	1.0000
15:45405506:G:GG	donor_gain	1.0000
15:45410355:T:TA	acceptor_gain	1.0000
15:45410356:G:A	acceptor_gain	1.0000
15:45410359:T:TA	acceptor_gain	1.0000
15:45410362:A:AG	acceptor_gain	1.0000
15:45410363:T:G	acceptor_gain	1.0000
15:45410370:A:AG	acceptor_gain	1.0000
15:45410370:A:AT	acceptor_loss	1.0000
15:45410371:G:GT	acceptor_gain	1.0000
15:45410371:GA:G	acceptor_gain	1.0000
15:45410371:GAA:G	acceptor_gain	1.0000
15:45410371:GAACC:G	acceptor_gain	1.0000
15:45410527:ACAG:A	donor_gain	1.0000
15:45410528:CAGG:C	donor_loss	1.0000
15:45410530:GGTAA:G	donor_loss	1.0000
15:45410531:G:GG	donor_gain	1.0000
15:45415759:G:GT	donor_gain	1.0000
15:45415778:GG:G	donor_gain	1.0000
15:45415779:GG:G	donor_gain	1.0000
15:45417260:T:TA	acceptor_gain	1.0000

AlphaMissense

4770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:45414668:A:T	K511I	0.994
15:45405352:A:C	R374S	0.983
15:45405352:A:T	R374S	0.983
15:45414669:A:C	K511N	0.982
15:45414669:A:T	K511N	0.982
15:45405453:T:C	L408P	0.981
15:45403170:G:C	K247N	0.980
15:45403170:G:T	K247N	0.980
15:45417360:A:C	R643S	0.980
15:45417360:A:T	R643S	0.980
15:45417359:G:C	R643T	0.976
15:45418663:T:C	L692P	0.976
15:45414650:G:A	G505E	0.975
15:45405473:G:C	A415P	0.974
15:45417310:G:C	A627P	0.974
15:45402962:T:A	V178D	0.971
15:45403285:T:C	F286L	0.969
15:45403287:C:A	F286L	0.969
15:45403287:C:G	F286L	0.969
15:45403456:G:C	A343P	0.969
15:45415711:T:C	L590P	0.969
15:45421043:G:C	A699P	0.969
15:45403151:G:A	G241E	0.968
15:45414641:T:C	L502P	0.968
15:45415636:A:T	E565V	0.968
15:45414649:G:T	G505W	0.967
15:45405351:G:C	R374T	0.965
15:45415626:T:C	F562L	0.964
15:45415628:T:A	F562L	0.964
15:45415628:T:G	F562L	0.964

dbSNP variants (sampled 300 via entrez): RS1000113778 (15:45419343 T>G), RS1000290783 (15:45406810 C>T), RS1000413483 (15:45412185 G>A,T), RS1000884952 (15:45405234 A>G,T), RS1000907833 (15:45407245 CT>C), RS1001129725 (15:45417990 G>A), RS1001169170 (15:45405396 G>A,C), RS1001236825 (15:45406856 G>A), RS1001499645 (15:45407941 A>G), RS1001517108 (15:45417593 T>C), RS1001641647 (15:45405664 A>G), RS1001686278 (15:45413491 C>A,G), RS1001739116 (15:45420748 C>G,T), RS1001771348 (15:45418298 C>G,T), RS1002014094 (15:45410131 T>C)

Disease associations

OMIM: gene MIM:619578 | disease phenotypes: MIM:612718, MIM:619616, MIM:619615

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with hearing loss and spasticity	Strong	Autosomal recessive
hearing loss, autosomal recessive 119	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hearing loss, autosomal recessive 119	Limited	AR

Mondo (3): AGAT deficiency (MONDO:0012996), neurodevelopmental disorder with hearing loss and spasticity (MONDO:0859206), hearing loss, autosomal recessive 119 (MONDO:0030480)

Orphanet (2): L-Arginine:glycine amidinotransferase deficiency (Orphanet:35704), Sensorineural hearing loss-spastic quadriplegia-intellectual disability syndrome (Orphanet:659975)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001332	Dystonia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002121	Generalized non-motor (absence) seizure
HP:0002510	Spastic tetraplegia
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0005280	Depressed nasal bridge
HP:0006970	Periventricular leukomalacia
HP:0007359	Focal-onset seizure
HP:0011099	Spastic hemiparesis
HP:0011463	Childhood onset
HP:0012469	Infantile spasms
HP:0032794	Myoclonic seizure

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000397_2	Renal function and chronic kidney disease	6.000000e-14
GCST000649_17	Chronic kidney disease	5.000000e-22
GCST001923_1	Glomerular filtration rate	8.000000e-10
GCST003790_2	Glomerular filtration rate	2.000000e-08
GCST003790_42	Glomerular filtration rate	5.000000e-12
GCST006586_35	Urinary albumin excretion	2.000000e-09
GCST007877_16	Creatinine levels	1.000000e-26
GCST008747_79	Estimated glomerular filtration rate	3.000000e-124
GCST009640_23	Urinary albumin-to-creatinine ratio	9.000000e-16
GCST012020_481	Serum metabolite levels	4.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0007778	urinary albumin to creatinine ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567192	Arginine-Glycine Amidinotransferase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067595 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tobacco Smoke Pollution	increases expression	2
TAK-243	increases sumoylation	1
deoxynivalenol	increases expression	1
manganese chloride	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression, increases expression	1
Testosterone	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1
Copper Sulfate	decreases expression	1
Magnetite Nanoparticles	increases 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
CHEMBL5576172	Binding	Induction of SPATA5L1 degradation in human LoVo cells at 1 uM incubated for 24 hrs by global proteomic profiling analysis	Discovery of the first ataxia telangiectasia and Rad3-related (ATR) degraders for cancer treatment. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns