ADD3

adducin 3, the group of Adducin family

Basic information

Region (hg38): 10:109996368-110135565

Previous symbols: [ "ADDL" ]

Links

ENSG00000148700

∙ NCBI:120 ∙ OMIM:601568 ∙ HGNC:245 ∙ Uniprot:Q9UEY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cerebral palsy, spastic quadriplegic, 3 (Limited), mode of inheritance: AR
spastic quadriplegic cerebral palsy (Supportive), mode of inheritance: AR
cerebral palsy, spastic quadriplegic, 3 (Strong), mode of inheritance: AR
complex neurodevelopmental disorder with motor features (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebral palsy, spastic quadriplegic, 3	AR	General	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	Neurologic	23836506

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADD3 gene.

not_provided (164 variants)
not_specified (80 variants)
Cerebral_palsy,_spastic_quadriplegic,_3 (6 variants)
ADD3-related_disorder (5 variants)
Complex_neurodevelopmental_disorder_with_motor_features (2 variants)
Cerebral_palsy (1 variants)
Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016824.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	45 clinvar		46
missense		1 clinvar	134 clinvar	9 clinvar	3 clinvar	147
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	137	54	3

Highest pathogenic variant AF is 0.00000867384

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADD3	protein_coding	protein_coding	ENST00000356080	14	139198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00120	125717	0	24	125741	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.330	363	381	0.952	0.0000191	4638
Missense in Polyphen		110	134.5	0.81785		1650
Synonymous	-0.103	135	133	1.01	0.00000684	1348
Loss of Function	5.04	4	37.2	0.108	0.00000207	430

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00107
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin. {ECO:0000269|PubMed:23836506}.;
Disease: DISEASE: Cerebral palsy, spastic quadriplegic 3 (CPSQ3) [MIM:617008]: A form of cerebral palsy, a group of non-progressive disorders of movement and/or posture resulting from defects in the developing central nervous system. CPSQ3 is an autosomal recessive neurodevelopmental disorder characterized by variable spasticity and cognitive impairment. {ECO:0000269|PubMed:23836506}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

pRec: 0.153

Intolerance Scores

loftool: 0.209
rvis_EVS: 0.16
rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

pHI: 0.719
hipred: N
hipred_score: 0.465
ghis: 0.508

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.190

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Add3
Phenotype: hematopoietic system phenotype; normal phenotype;

Zebrafish Information Network

Gene name: add3a
Affected structure: intrahepatic bile duct
Phenotype tag: abnormal
Phenotype quality: decreased length

Gene ontology

Biological process: barbed-end actin filament capping;actin filament bundle assembly;transmembrane transport
Cellular component: condensed nuclear chromosome;nucleoplasm;cytosol;cytoskeleton;plasma membrane;brush border;cell-cell junction;cell cortex;postsynaptic density;membrane;plasma membrane raft
Molecular function: structural molecule activity;structural constituent of cytoskeleton;calmodulin binding;spectrin binding;actin filament binding