ICE2

protein-coding

interactor of little elongation complex ELL subunit 2

Gene summary

This gene encodes a protein component of the little elongation complex (LEC), which plays a role in small nuclear RNA (snRNA) transcription. The LEC regulates snRNA transcription by enhancing both RNA Polymerase II occupancy and transcriptional elongation. The encoded protein and other LEC components have been shown to localize to Cajal bodies, which are sites of ribonucleoprotein (RNP) complex assembly. Pseudogenes of this gene have been identified on chromosomes 3 and 4. [provided by RefSeq, May 2017]

Previous symbols:

NARG2

MANE transcript

NM_024611.6

Inheritance

—

ClinVar variants

U:152B:19

Top phenotype

ICE2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr15:60,419,609-60,479,160

External References & Databases

Ensembl (ENSG00000128915)

Transcript & Mutation Effects

hg38 • Region Span ~59.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ICE2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 147

ICE2-related disorderTotal: 13

not providedTotal: 9

NARG2-related Intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024611.6. 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	7 clinvar	2 clinvar	10
missense			148 clinvar	8 clinvar	2 clinvar	158
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	152	15	4	171

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024611.6	RefSeq	NP_078887.2	15	MANE Select
ENST00000261520.9	Ensembl	ENSP00000261520.4	15	MANE Select
NM_001018089.3	RefSeq	NP_001018099.1	12	Standard
NM_001276385.2	RefSeq	NP_001263314.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
RNA polymerase II transcribes snRNA genes
RNA Polymerase II Transcription

Biological Process

snRNA transcription by RNA polymerase II
snRNA transcription by RNA polymerase III
positive regulation of transcription by RNA polymerase III

Molecular Function

protein binding

Cellular Component

nucleoplasm
cytosol
transcription elongation factor complex
Cajal body
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261520
Coding exons: 15
Length: 59552
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125748
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.906	554	497	1.11	0.0000245	6409
Missense (PolyPhen)		165	162.84	1.0133		2273
Synonymous	-0.672	187	176	1.06	0.00000887	1845
Loss of Function	2.44	28	45.8	0.612	0.00000246	630

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00025	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00056	0.00054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00035	0.00034	rare
South Asian	0.00031	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. {ECO:0000269|PubMed:23932780}.;

Recessive Scores

pRec: 0.168

Intolerance Scores

RVIS EVS: -0.82
RVIS percentile EVS: 12.01

Essentials

Essential (gene trap): H