AFG2B

protein-coding

AFG2 AAA ATPase homolog B, the group of AAA ATPases

Gene summary

Enables identical protein binding activity and preribosome binding activity. Involved in DNA replication; regulation of ribosome biogenesis; and ribosomal large subunit biogenesis. Located in cytoplasm; nucleus; and spindle. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

SPATA5L1

MANE transcript

NM_024063.3

Inheritance

ClinVar variants

P:23U:130B:18

Top phenotype

Deafness, autosomal recessive 119; Neurodevelopmental disorder with hearing loss and spasticity

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr15:45,402,336-45,421,415

External References & Databases

Ensembl (ENSG00000171763)

Transcript & Mutation Effects

hg38 • Region Span ~19.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessive 119LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030480

Submitter: ClinGen

AFG2B/SPATA5L1 was first reported in relation to autosomal recessive deafness 119 (DFNB119) in 2021 (Richard et al.; PMID: 34626583). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found clear differences in phenotypic variability. Therefore, the following disease entities have been split into two disease entities, DFNB119 (OMIM: 619615) and autosomal recessive neurodevelopmental disorder with hearing loss and spasticity (NEDHLS; OMIM: 619616). The split curation for NEDHLS has been done separately. 4 variants (missense, frameshift) that have been reported in over 20 probands in one publication (PMID: 34626583) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by expression-level evidence (PMID: 34626583; GTEx expression data). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role of AFG2B/SPATA5L1 in isolated hearing loss, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Hearing Loss GCEP on the meeting date 2/21/2024 (SOP Version 10).

neurodevelopmental disorder with hearing loss and spasticityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859206

Submitter: Ambry Genetics

hearing loss, autosomal recessive 119STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030480

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with hearing loss and spasticityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859206

Submitter: G2P

hearing loss, autosomal recessive 119STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030480

Submitter: PanelApp Australia

neurodevelopmental disorder with hearing loss and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859206

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 119; Neurodevelopmental disorder with hearing loss and spasticityAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 34626583

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AFG2B variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 107

not providedTotal: 43

Neurodevelopmental disorder with hearing loss and spasticityTotal: 20

Hearing loss, autosomal recessive 119Total: 10

SPATA5L1-associated disorderTotal: 7

AFG2B-related disorderTotal: 6

See casesTotal: 6

not specifiedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024063.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	10 clinvar		13
missense	1 clinvar	13 clinvar	124 clinvar	6 clinvar	2 clinvar	146
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss			1 clinvar			1
frameshift	4 clinvar	2 clinvar				6
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	7	16	130	16	2	171

Highest pathogenic variant AF is 0.0014405289

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024063.3	RefSeq	NP_076968.2	8	MANE Select
ENST00000305560.11	Ensembl	ENSP00000305494.6	8	MANE Select
NM_001323640.2	RefSeq	NP_001310569.1	5	Standard
ENST00000525552.1	Ensembl	ENSP00000453091.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

ATP binding
ATPase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305560
Coding exons: 8
Length: 19089
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 125748
p: 0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.861	346	394	0.878	0.0000190	4685
Missense (PolyPhen)		94	115.98	0.81051		1376
Synonymous	0.480	162	170	0.953	0.00000872	1691
Loss of Function	1.28	20	27.2	0.735	0.00000158	303

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00053	0.00052	rare
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00099	0.00098	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00041	0.00040	rare
South Asian	0.00027	0.00026	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0896

Intolerance Scores

LoFtool: 0.211
RVIS EVS: -0.22
RVIS percentile EVS: 37.54

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High