ANKS1B

protein-coding

ankyrin repeat and sterile alpha motif domain containing 1B, the group of Ankyrin repeat domain containing|Sterile alpha motif domain containing

Gene summary

This gene encodes a multi-domain protein that is predominantly expressed in brain and testis. This protein interacts with amyloid beta protein precursor (AbetaPP) and may have a role in normal brain development, and in the pathogenesis of Alzheimer's disease. Expression of this gene has been shown to be elevated in patients with pre-B cell acute lymphocytic leukemia associated with t(1;19) translocation. Alternatively spliced transcript variants encoding different isoforms (some with different subcellular localization, PMID:15004329) have been described for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001352186.2

Inheritance

ClinVar variants

P:1U:116B:20

Top phenotype

ANKS1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr12:98,726,457-99,984,936

External References & Databases

Ensembl (ENSG00000185046)

Transcript & Mutation Effects

hg38 • Region Span ~1,258.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Illumina

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ANKS1B variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 133

not providedTotal: 29

ANKS1B-related disorderTotal: 5

ANKS1B-related neurodevelopmental disorderTotal: 1

Normal pregnancyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001352186.2. 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				6 clinvar	4 clinvar	10
missense			108 clinvar	8 clinvar	2 clinvar	118
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	0	1	116	14	6	137

Highest pathogenic variant AF is 7.177597e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 100 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001352186.2	RefSeq	NP_001339115.1	27	MANE Select
ENST00000683438.2	Ensembl	ENSP00000508105.1	27	MANE Select
NM_001204065.2	RefSeq	NP_001190994.1	9	Standard
NM_001204066.2	RefSeq	NP_001190995.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation

Biological Process

regulation of synaptic plasticity by receptor localization to synapse

Molecular Function

ephrin receptor binding

Cellular Component

cytosol
plasma membrane
postsynaptic density
Cajal body
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000547776
Coding exons: 26
Length: 1258198
Individuals with no LoFs: 124624
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 124635
p: 0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	432	642	0.673	0.0000320	8139
Missense (PolyPhen)		74	193.06	0.38329		2446
Synonymous	0.292	239	245	0.976	0.0000134	2416
Loss of Function	6.41	7	61.1	0.115	0.00000317	774

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000028	0.000027	rare
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.; FUNCTION: Isoform 4 may play a role as a modulator of APP processing. Overexpression can down-regulate APP processing.;

Recessive Scores

pRec: 0.210

Intolerance Scores

LoFtool: 0.269
RVIS EVS: -1.22
RVIS percentile EVS: 5.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.595

Gene Damage Prediction

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