CDIN1

protein-coding

CDAN1 interacting nuclease 1

Gene summary

This gene encodes a protein with two predicted helix-turn-helix domains. Mutations in this gene were found in families with congenital dyserythropoietic anemia type Ib. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Previous symbols:

C15orf41

MANE transcript

NM_001321759.2

Inheritance

ClinVar variants

P:4U:47B:28

Top phenotype

Congenital dyserythropoietic anemia type Ib

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr15:36,579,626-36,810,248

External References & Databases

Ensembl (ENSG00000186073)

Transcript & Mutation Effects

hg38 • Region Span ~230.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital dyserythropoietic anemia type 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020337

Submitter: Orphanet

congenital dyserythropoietic anemia type type 1BSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014285

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Congenital dyserythropoietic anemia type IbAR

Manifestation: Hematologic; Musculoskeletal

Intervention: Hematologic

Rationale: Individuals have been described as manifesting with early childhood onset, severe anemia requiring treatment via RBC transfusion

Refs: 9220189; 16643456; 16754775; 23716552

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDIN1 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 96

not specifiedTotal: 16

Congenital dyserythropoietic anemia type type 1BTotal: 16

CDIN1-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321759.2. 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			1 clinvar	23 clinvar	2 clinvar	26
missense		4 clinvar	40 clinvar	3 clinvar		47
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	4	47	26	2	79

Highest pathogenic variant AF is 0.0000062060226

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321759.2	RefSeq	NP_001308688.1	11	MANE Select
ENST00000566621.6	Ensembl	ENSP00000455397.1	11	MANE Select
NM_001130010.3	RefSeq	NP_001123482.1	11	Standard
NM_001290232.2	RefSeq	NP_001277161.1	7	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000566621
Coding exons: 11
Length: 230638
Individuals with no LoFs: 124627
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 124654
p: 0.000108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.473	129	145	0.890	0.00000722	1825
Missense (PolyPhen)		41	48.36	0.84781		603
Synonymous	1.15	46	57.0	0.807	0.00000319	510
Loss of Function	1.38	13	19.6	0.664	9.22e-7	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000095	0.000093	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Anemia, congenital dyserythropoietic, 1B (CDAN1B) [MIM:615631]: An autosomal recessive blood disorder characterized by morphological abnormalities of erythroblasts, ineffective erythropoiesis, macrocytic anemia and secondary hemochromatosis. It is occasionally associated with bone abnormalities, especially of the hands and feet (acrodysostosis), nail hypoplasia, and scoliosis. Ultrastructural features include internuclear chromatin bridges connecting some nearly completely separated erythroblasts and an abnormal appearance (spongy or Swiss-cheese appearance) of the heterochromatin in a high proportion of the erythroblasts. {ECO:0000269|PubMed:23716552}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.614
RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E

Gene Damage Prediction

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