SOBP

protein-coding

sine oculis binding protein homolog

Gene summary

The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

MANE transcript

NM_018013.4

Inheritance

ClinVar variants

U:150B:42

Top phenotype

Impaired intellectual development, anterior maxillary protrusion, and strabismus

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:107,490,106-107,661,306

External References & Databases

Ensembl (ENSG00000112320)

Transcript & Mutation Effects

hg38 • Region Span ~171.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

impaired intellectual development, anterior maxillary protrusion, and strabismusLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013353

Submitter: PanelApp Australia

syndromic intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0000508

Submitter: ClinGen

Variants in *SOBP* were first reported in a single consanguineous family with autosomal recessive syndromic intellectual disability in 2010 (Brik et al., PMID: 21035105). Affected individuals in this family exhibited intellectual disability, dysmorphic features, and strabismus. The condition was referred to by the authors as MRAMS syndrome (for mental retardation, anterior maxillary protrusion, and strabismus, OMIM: 613671) (Vanagaite et al., PMID: 17618476). Given the phenotypic variability of the syndromic neurodevelopmental features of affected individuals, we opted to curate this gene for syndromic intellectual disability. At this time, a single nonsense variant has been reported in one proband (PMID: 21035105). This variant segregated with disease in six additional family members. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on October 18, 2022. It was reevaluated on October 1, 2026. As a result of this reevaluation, no additional patients were identified and the classification did not change. The scoring was updated to be consistent with SOP Version 12.

impaired intellectual development, anterior maxillary protrusion, and strabismusLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013353

Submitter: Labcorp Genetics (formerly Invitae)

impaired intellectual development, anterior maxillary protrusion, and strabismusSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013353

Submitter: Orphanet

impaired intellectual development, anterior maxillary protrusion, and strabismusLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013353

Submitter: G2P

Clinical Genomic Database (CGD)

Impaired intellectual development, anterior maxillary protrusion, and strabismusAR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 17618476; 21035105

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOBP variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 155

not providedTotal: 50

Intellectual disability, anterior maxillary protrusion, and strabismusTotal: 10

SOBP-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018013.4. 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			8 clinvar	33 clinvar	1 clinvar	42
missense			139 clinvar	7 clinvar	1 clinvar	147
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	150	40	2	192

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018013.4	RefSeq	NP_060483.3	6	MANE Select
ENST00000317357.10	Ensembl	ENSP00000318900.5	6	MANE Select
ENST00000618129.1	Ensembl	ENSP00000478366.1	4	Standard
ENST00000618129.2	Ensembl	ENSP00000478366.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sensory perception of sound
locomotory behavior
inner ear morphogenesis
cognition
cochlea development

Molecular Function

SUMO polymer binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317357
Coding exons: 6
Length: 170196
Individuals with no LoFs: 124692
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124697
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.92	365	484	0.754	0.0000307	5616
Missense (PolyPhen)		145	233.22	0.62173		2577
Synonymous	0.616	215	227	0.948	0.0000176	1833
Loss of Function	4.48	0	23.4	0.00	0.00000130	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Implicated in development of the cochlea. {ECO:0000250|UniProtKB:Q0P5V2}.;
Disease: DISEASE: Mental retardation, anterior maxillary protrusion, and strabismus (MRAMS) [MIM:613671]: A syndrome characterized by severe mental retardation, strabismus and dysmorphic features such as anterior maxillary protrusion with vertical maxillary excess, open bite and prominent crowded teeth. Some patients may lack dysmorphic features and manifest temporal lobe epilepsy and psychosis. Esotropia and amblyopia are present in some individuals. {ECO:0000269|PubMed:21035105}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.0220
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.578

Gene Damage Prediction

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