Mutagenetix > Incidental Mutation

Incidental Mutation 'N/A - 535:Lifr'

210

Institutional Source

Beutler Lab

Gene Symbol

Lifr

Ensembl Gene

ENSMUSG00000054263

Gene Name

LIF receptor alpha

Synonyms

soluble differentiation-stimulating factor receptor, A230075M04Rik

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

N/A - 535 of strain bumble

Quality Score

Status

Validated

Chromosome

Chromosomal Location

7120095-7226970 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 7216434 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 803 (H803L)

Ref Sequence

ENSEMBL: ENSMUSP00000154750 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000067190] [ENSMUST00000164529] [ENSMUST00000171588] [ENSMUST00000226471] [ENSMUST00000226934] [ENSMUST00000227727]

AlphaFold

P42703

Predicted Effect

possibly damaging
Transcript: ENSMUST00000067190
AA Change: H803L

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000064551
Gene: ENSMUSG00000054263
AA Change: H803L

Domain	Start	End	E-Value	Type
low complexity region	25	37	N/A	INTRINSIC
Blast:FN3	45	118	5e-22	BLAST
FN3	328	399	1.86e1	SMART
FN3	425	515	9.77e-5	SMART
FN3	530	611	2.68e0	SMART
FN3	620	705	8.23e1	SMART
FN3	719	815	4.81e-4	SMART
transmembrane domain	830	852	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000164529

SMART Domains

Protein: ENSMUSP00000131434
Gene: ENSMUSG00000054263

Domain	Start	End	E-Value	Type
low complexity region	25	37	N/A	INTRINSIC
Blast:FN3	45	118	4e-22	BLAST
FN3	328	399	1.86e1	SMART
FN3	425	515	9.77e-5	SMART
FN3	530	611	2.68e0	SMART
FN3	620	705	8.23e1	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000171588
AA Change: H803L

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000126137
Gene: ENSMUSG00000054263
AA Change: H803L

Domain	Start	End	E-Value	Type
low complexity region	25	37	N/A	INTRINSIC
Blast:FN3	45	118	5e-22	BLAST
FN3	328	399	1.86e1	SMART
FN3	425	515	9.77e-5	SMART
FN3	530	611	2.68e0	SMART
FN3	620	705	8.23e1	SMART
FN3	719	815	4.81e-4	SMART
transmembrane domain	830	852	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000226471
AA Change: H803L

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

Predicted Effect

probably benign
Transcript: ENSMUST00000226934

Predicted Effect

probably benign
Transcript: ENSMUST00000227727

Meta Mutation Damage Score

0.0670

Coding Region Coverage

1x: 83.1%
3x: 57.4%

Validation Efficiency

88% (80/91)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that belongs to the type I cytokine receptor family. This protein combines with a high-affinity converter subunit, gp130, to form a receptor complex that mediates the action of the leukemia inhibitory factor, a polyfunctional cytokine that is involved in cellular differentiation, proliferation and survival in the adult and the embryo. Mutations in this gene cause Schwartz-Jampel syndrome type 2, a disease belonging to the group of the bent-bone dysplasias. A translocation that involves the promoter of this gene, t(5;8)(p13;q12) with the pleiomorphic adenoma gene 1, is associated with salivary gland pleiomorphic adenoma, a common type of benign epithelial tumor of the salivary gland. Multiple splice variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations die as neonates with reduced numbers of facial and spinal motor neurons, neurons of the nucleus ambiguus, and astrocytes. Mutants also show impaired placentation, severe osteopenia, and low hepatic glycogen stores. [provided by MGI curators]

Allele List at MGI

All alleles(22) : Targeted, knock-out(1) Targeted, other(2) Gene trapped(19)

Other mutations in this stock

Total: 11 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cacna1e	A	T	1: 154,341,510 (GRCm39)	L1166Q	probably damaging	Het
Cd44	T	C	2: 102,644,534 (GRCm39)	M481V	possibly damaging	Het
Eif4g3	T	A	4: 137,847,739 (GRCm39)	V220D	probably damaging	Het
Gm12778	T	A	7: 33,875,347 (GRCm39)		noncoding transcript	Homo
Klhl29	C	T	12: 5,134,019 (GRCm39)	A773T	probably damaging	Homo
Macf1	T	C	4: 123,367,601 (GRCm39)	T822A	possibly damaging	Het
Obscn	A	T	11: 58,891,134 (GRCm39)	C1653S	possibly damaging	Het
Ogdh	T	C	11: 6,274,911 (GRCm39)	L180P	possibly damaging	Het
Rnf5	T	C	17: 34,822,330 (GRCm39)	S40G	possibly damaging	Het
Sbf2	T	C	7: 109,911,959 (GRCm39)	T1696A	probably benign	Het
Ska2	C	T	11: 87,008,680 (GRCm39)		probably benign	Het

Other mutations in Lifr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00702:Lifr	APN	15	7,215,220 (GRCm39)	splice site	probably null
IGL01470:Lifr	APN	15	7,205,147 (GRCm39)	nonsense	probably null
IGL01489:Lifr	APN	15	7,205,037 (GRCm39)	splice site	probably benign
IGL01619:Lifr	APN	15	7,220,643 (GRCm39)	missense	probably damaging	1.00
IGL01636:Lifr	APN	15	7,208,499 (GRCm39)	splice site	probably benign
IGL01943:Lifr	APN	15	7,217,630 (GRCm39)	missense	probably damaging	1.00
IGL02253:Lifr	APN	15	7,220,085 (GRCm39)	missense	probably damaging	1.00
IGL02355:Lifr	APN	15	7,194,174 (GRCm39)	critical splice donor site	probably null
IGL02362:Lifr	APN	15	7,194,174 (GRCm39)	critical splice donor site	probably null
IGL02450:Lifr	APN	15	7,220,246 (GRCm39)	missense	probably damaging	1.00
IGL02477:Lifr	APN	15	7,216,404 (GRCm39)	missense	probably damaging	1.00
IGL02503:Lifr	APN	15	7,215,104 (GRCm39)	missense	probably damaging	1.00
IGL02571:Lifr	APN	15	7,219,592 (GRCm39)	unclassified	probably benign
IGL03340:Lifr	APN	15	7,207,417 (GRCm39)	missense	probably benign	0.02
R0012:Lifr	UTSW	15	7,205,089 (GRCm39)	missense	possibly damaging	0.78
R0015:Lifr	UTSW	15	7,217,667 (GRCm39)	splice site	probably null
R0102:Lifr	UTSW	15	7,208,373 (GRCm39)	missense	probably damaging	0.98
R0102:Lifr	UTSW	15	7,208,373 (GRCm39)	missense	probably damaging	0.98
R0305:Lifr	UTSW	15	7,206,982 (GRCm39)	missense	probably damaging	0.99
R0416:Lifr	UTSW	15	7,196,395 (GRCm39)	missense	probably damaging	1.00
R0440:Lifr	UTSW	15	7,186,672 (GRCm39)	nonsense	probably null
R0519:Lifr	UTSW	15	7,207,061 (GRCm39)	missense	probably damaging	1.00
R0595:Lifr	UTSW	15	7,206,950 (GRCm39)	missense	probably damaging	1.00
R0601:Lifr	UTSW	15	7,198,753 (GRCm39)	splice site	probably null
R0780:Lifr	UTSW	15	7,206,947 (GRCm39)	missense	probably benign	0.00
R0790:Lifr	UTSW	15	7,215,196 (GRCm39)	missense	probably benign	0.13
R1376:Lifr	UTSW	15	7,214,245 (GRCm39)	missense	probably benign	0.04
R1376:Lifr	UTSW	15	7,214,245 (GRCm39)	missense	probably benign	0.04
R1400:Lifr	UTSW	15	7,220,346 (GRCm39)	missense	probably benign	0.04
R1498:Lifr	UTSW	15	7,220,099 (GRCm39)	missense	probably damaging	0.99
R1785:Lifr	UTSW	15	7,211,337 (GRCm39)	missense	possibly damaging	0.89
R1786:Lifr	UTSW	15	7,211,337 (GRCm39)	missense	possibly damaging	0.89
R1906:Lifr	UTSW	15	7,217,612 (GRCm39)	missense	probably damaging	0.98
R2099:Lifr	UTSW	15	7,186,732 (GRCm39)	missense	probably benign
R2102:Lifr	UTSW	15	7,216,404 (GRCm39)	missense	probably damaging	1.00
R2136:Lifr	UTSW	15	7,211,338 (GRCm39)	missense	possibly damaging	0.89
R2511:Lifr	UTSW	15	7,196,397 (GRCm39)	missense	probably benign
R4375:Lifr	UTSW	15	7,196,379 (GRCm39)	missense	probably benign
R4883:Lifr	UTSW	15	7,215,106 (GRCm39)	missense	possibly damaging	0.94
R5681:Lifr	UTSW	15	7,220,565 (GRCm39)	missense	probably damaging	1.00
R5689:Lifr	UTSW	15	7,214,285 (GRCm39)	missense	probably damaging	1.00
R5693:Lifr	UTSW	15	7,205,041 (GRCm39)	missense	probably damaging	1.00
R5902:Lifr	UTSW	15	7,220,231 (GRCm39)	missense	probably benign
R5918:Lifr	UTSW	15	7,188,897 (GRCm39)	missense	probably benign	0.00
R5924:Lifr	UTSW	15	7,202,453 (GRCm39)	missense	probably benign	0.28
R6037:Lifr	UTSW	15	7,216,424 (GRCm39)	missense	probably damaging	1.00
R6037:Lifr	UTSW	15	7,216,424 (GRCm39)	missense	probably damaging	1.00
R6289:Lifr	UTSW	15	7,196,391 (GRCm39)	missense	probably benign	0.00
R6339:Lifr	UTSW	15	7,196,530 (GRCm39)	missense	probably benign	0.01
R6860:Lifr	UTSW	15	7,202,418 (GRCm39)	missense	probably benign	0.02
R7106:Lifr	UTSW	15	7,202,405 (GRCm39)	missense	probably benign	0.02
R7107:Lifr	UTSW	15	7,208,421 (GRCm39)	missense	possibly damaging	0.88
R7274:Lifr	UTSW	15	7,196,540 (GRCm39)	critical splice donor site	probably null
R7625:Lifr	UTSW	15	7,198,723 (GRCm39)	missense	probably damaging	0.99
R7631:Lifr	UTSW	15	7,214,258 (GRCm39)	missense	probably damaging	1.00
R7958:Lifr	UTSW	15	7,211,478 (GRCm39)	missense	possibly damaging	0.62
R7991:Lifr	UTSW	15	7,202,963 (GRCm39)	missense	possibly damaging	0.79
R8175:Lifr	UTSW	15	7,216,496 (GRCm39)	missense	probably damaging	1.00
R8427:Lifr	UTSW	15	7,220,462 (GRCm39)	missense	probably benign	0.01
R9274:Lifr	UTSW	15	7,217,591 (GRCm39)	missense	probably damaging	0.98
R9311:Lifr	UTSW	15	7,208,418 (GRCm39)	missense	possibly damaging	0.47
R9365:Lifr	UTSW	15	7,198,521 (GRCm39)	missense	probably damaging	1.00
R9509:Lifr	UTSW	15	7,188,955 (GRCm39)	missense	probably damaging	0.99

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at position 2472 of the Lifr transcript in exon 20 of 23 total exons. The mutated nucleotide causes a histidine to leucine substitution at amino acid 803 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Lifr gene encodes a 1092 amino acid receptor that transduces signals upon binding to leukemia inhibitory factor (LIF). A soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells. LIFR can form a heterodimer with the beta subunit of the interleukin 6 (IL6) receptor, and contains six fibronectin type III domains and a Janus kinase (JAK) interacting box 1 motif (Uniprot P42703 ). Mice homozygous for targeted null mutations die as neonates with reduced numbers of facial and spinal motor neurons, neurons of the nucleus ambiguus, and astrocytes. Mutants also show impaired placentation, severe osteopenia, and low hepatic glycogen stores.

The H803L change occurs in the extracellular region in the sixth fibronectin type III domain, and is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-05-04