ADD1

protein-coding

adducin 1, the group of Adducin family

Gene summary

Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]

MANE transcript

NM_001354761.2

Inheritance

ClinVar variants

P:1U:101B:14

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr4:2,843,844-2,930,076

External References & Databases

Ensembl (ENSG00000087274)

Transcript & Mutation Effects

hg38 • Region Span ~86.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADD1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 14

ADD1-related disorderTotal: 2

Essential hypertension, geneticTotal: 1

ADD1-related intellectual disability, corpus callosum dysgenesis, and ventriculomegalyTotal: 1

Neurodevelopmental disorderTotal: 1

Esophageal atresia/tracheoesophageal fistulaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001354761.2. 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			4 clinvar	5 clinvar	6 clinvar	15
missense			93 clinvar	2 clinvar	1 clinvar	96
nonsense			1 clinvar			1
start loss		1 clinvar				1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	101	7	7	116

Highest pathogenic variant AF is 6.9637207e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 127 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001354761.2	RefSeq	NP_001341690.1	15	MANE Select
ENST00000683351.1	Ensembl	ENSP00000508142.1	15	MANE Select
NM_001119.5	RefSeq	NP_001110.2	14	Standard
NM_001286645.2	RefSeq	NP_001273574.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Diuretics Pathway, Pharmacodynamics
XBP1(S) activates chaperone genes
Caspase-mediated cleavage of cytoskeletal proteins
Apoptotic cleavage of cellular proteins
Apoptotic execution phase

Biological Process

cell morphogenesis
in utero embryonic development
cell volume homeostasis
hemoglobin metabolic process
actin cytoskeleton organization

Molecular Function

RNA binding
actin binding
structural molecule activity
calmodulin binding
transcription factor binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264758
Coding exons: 14
Length: 86220
Individuals with no LoFs: 125513
Homozygous LoFs: 0
Heterozygous LoFs: 235
Defined: 125748
p: 0.000935

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.804	401	449	0.893	0.0000264	5011
Missense (PolyPhen)		154	195.46	0.7879		2220
Synonymous	1.30	163	185	0.879	0.0000127	1520
Loss of Function	4.74	5	35.5	0.141	0.00000182	433

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.0055	0.0055	notable
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.0023	0.0023	notable
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.;

Recessive Scores

pRec: 0.390

Intolerance Scores

LoFtool: 0.669
RVIS EVS: -0.93
RVIS percentile EVS: 9.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.582

Gene Damage Prediction

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